gfp927z
3週前
>>> Acurx Receives Positive Regulatory Guidance from EMA for Ibezapolstat Phase 3 Program for C. Difficile Infection (CDI)
PR Newswire
January 6, 2025
https://finance.yahoo.com/news/acurx-receives-positive-regulatory-guidance-133000707.html
Acurx has now received positive written responses from the EMA (European Medicines Agency) under its Scientific Advice Procedure that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted supports advancement of the ibezapolstat Phase 3 program
The responses also included guidance on ibezapolstat's regulatory pathway for a Marketing Authorization Application for ibezapolstat in CDI
With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program
Acurx is also preparing to request regulatory guidance to initiate clinical trials in Japan, Canada and the United Kingdom
Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designation from FDA and Acurx has received SME (Small and Medium-sized Enterprise) designation by the EMA to benefit from fee incentives and other support from the EMA for EU Marketing Authorization
STATEN ISLAND, N.Y., Jan. 6, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company") is a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, with its lead antibiotic candidate, ibezapolstat, preparing to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). The Company today announced that it has received positive regulatory guidance from the EMA during its Scientific Advice Procedure that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted supports advancement of the ibezapolstat Phase 3 program. The information package supporting the Phase 3 program included details on Acurx's two planned Phase 3 clinical trials (designed as non-inferiority trials vs vancomycin), the patient population, primary endpoint of Clinical Cure, sample size, statistical analysis plan and the overall registration safety database.
Acurx's Executive Chairman, Bob DeLuccia, stated: "We are appreciative of the EMA's constructive suggestions, and we will proactively incorporate them into our global registration plan. He further stated: "We are very pleased with the latest favorable communications from both regulatory agencies which provide a straightforward international roadmap for conduct of our Phase 3 program and ultimate requirements for a US NDA (New Drug Application) submission and EU Marketing Authorization Application."
Written communications are used by both regulatory agencies in lieu of face-to-face or teleconference/video conferences when these agencies determine that a written response to the sponsor's questions would be the most appropriate means for providing feedback and advice to the sponsor. (FDA Guidance on Formal Meetings, EMA Guidance on Centralised Procedure)
Acurx previously announced it had a successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, including written positive feedback regarding acceptability of its CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program. In addition, Acurx had initiated the Scientific Advice procedure with the EMA to discuss the readiness for initiation of the Phase 3 clinical program in the EU. Acurx is preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, to be followed by requests to be submitted in the United Kingdom, Japan and Canada.
Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (Link to Clinicaltrials.gov/NCT042447542) This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In the Phase 2a trial segment,10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment).
In the Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug- related. All three events were gastrointestinal in nature and resolved without treatment.
There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022).
In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection. Furthermore, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015,
New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022). In the Ph2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), drug-resistant Streptococcus pneumoniae (DRSP) and B. anthracis (anthrax; a Bioterrorism Category A Threat-Level pathogen). Acurx's lead product candidate, ibezapolstat, for the treatment of C. difficile Infection is Phase 3 ready with plans in progress to begin international clinical trials next year. The Company's preclinical pipeline includes development of an oral product candidate for treatment of ABSSSI (Acute Bacterial Skin and Skin Structure Infections), upon which a development program for treatment of inhaled anthrax is being planned in parallel.
gfp927z
2月前
>>> Acurx Updates Phase 3 Readiness for Ibezapolstat in C. difficile Infection Based on Recent FDA and EMA Communications
PR Newswire
December 9, 2024
https://finance.yahoo.com/news/acurx-updates-phase-3-readiness-130000907.html
Following the previously announced successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, Acurx has now also received written positive feedback from FDA regarding acceptability of our CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program
Acurx has initiated the Scientific Advice procedure with the European Medicines Agency (EMA) to discuss the readiness for initiation of the Phase 3 clinical program in the European Union (EU). Acurx has been notified that we should expect to receive the final written advice letter in the coming few weeks
Acurx is also in the process of discussing the pediatric development plans for ibezapolstat in C. difficile Infection with FDA and EU health authorities, per regulatory requirements.
Phase 3 international trial planning continues to advance, using AI and other state-of-the-art techniques to identify and qualify clinical trial sites with the highest potential for patient enrollment
Acurx is also preparing to request regulatory guidance to initiate clinical trials in Japan, Canada and the United Kingdom
Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designation from FDA and Acurx has received SME (Small and Medium-sized Enterprise) designation by the EMA to benefit from fee incentives and other support from the EMA for EU Marketing Authorization
STATEN ISLAND, N.Y., Dec. 9, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, with its lead antibiotic candidate, ibezapolstat, preparing to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). The Company today announced updates on Phase 3 Readiness for Ibezapolstat in C. difficile Infection based on recent FDA and EMA Communications.
Written communications are used by both regulatory agencies in lieu of face-to-face or teleconference/video conferences when these agencies determine that a written response to the sponsor's questions would be the most appropriate means for providing feedback and advice to the sponsor. (FDA Guidance on Formal Meetings, EMA Guidance on Centralised Procedure)
Acurx's Executive Chairman, Bob DeLuccia, stated: "We are very pleased with these latest favorable communications from both regulatory agencies and in our opinion are a testament to the strength of our clinical data to date, our robust regulatory submissions, and adherence to current regulatory guidance." He further added: "We anticipate, and are confident, that with final EMA advice for our ibezapolstat Phase 3 trials for adult patients with CDI and the pediatric development plans from both regulatory agencies, Acurx will have a clear international roadmap for conduct of our Phase 3 program and, if successful, requirements for US NDA submission and EU Marketing Authorization."
Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, to be followed by requests to be submitted in the United Kingdom, Japan and Canada.
Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-reat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (Link to Clinicaltrials.gov/NCT042447542) This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In the Phase 2a trial segment,10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment).
In the Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug- related. All three events were gastrointestinal in nature and resolved without treatment.
There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022).
In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection. Furthermore, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi: 0.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022). In the Ph2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), drug-resistant Streptococcus pneumoniae (DRSP) and B. anthracis (anthrax; a Bioterrorism Category A Threat-Level pathogen). Acurx's lead product candidate, ibezapolstat, for the treatment of C. difficile Infection is Phase 3 ready with plans in progress to begin international clinical trials next year. The Company's preclinical pipeline includes development of an oral product candidate for treatment of ABSSSI (Acute Bacterial Skin and Skin Structure Infections), upon which a development program for treatment of inhaled anthrax is being planned in parallel.
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gfp927z
4月前
>>> Acurx Announces Additional Ibezapolstat Ph2b Results in CDI as well as Anthrax (B. anthracis) Susceptibility to ACX-375 Analogues
PR Newswire
September 26, 2024
https://finance.yahoo.com/news/acurx-announces-additional-ibezapolstat-ph2b-110000237.html
New analyses extend data on beneficial effects of ibezapolstat on the gut microbiome
Confirmed ibezapolstat's favorable pharmacokinetics showing low systemic exposure and high colonic concentrations
Selected ACX-375 analogues demonstrated in vitro activity against Anthrax (B. anthracis), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant Anthrax. Planning is underway for an Anthrax bioterrorism development program
Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)
Preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA
STATEN ISLAND, N.Y., Sept. 26, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced results from new analyses that extend data on the beneficial effects of ibezapolstat on the gut microbiome. The data show an increased proportion of Actinobacteriota and increased quantity of beneficial Bacillota (Firmicutes) leading to reversal of dysbiosis and contributing to the CDI anti-recurrence effect of ibezapolstat.
Additionally, ibezapolstat's favorable pharmacokinetics properties were confirmed showing mean systemic exposure below 1mcg/mL and fecal concentrations well in excess of the minimal inhibitory concentration (MIC) for C. difficile.
Microbiological testing of certain ACX-375 DNA pol IIIC analogues in independent qualified laboratories, including the University of Florida, demonstrated in vitro activity with MICs of 0.5-2mcg/mL against B. anthracis (Anthrax), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant B. anthracis.
The above results were presented at the premier International C. difficile Symposium (ICDS) held in Bled, Slovenia on September 17-19, 2024. Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program, and Acurx Scientific Advisory Board member delivered a presentation entitled: Ibezapolstat Preserves Key Clostridium leptum Species. Microbiome Results from the Phase 2, Randomized, Double-blind Study of ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides Difficile Infection.
According to Dr. Garey: "The microbiome data also show an unexpected finding of a unique microbiome signature in two vancomycin-treated patients in the Ph2b trial who experienced recurrence of CDI. Since these changes were evident and observed early during treatment and then consistently until the end of therapy, they may be predictive of pending CDI recurrence and suggest the need to modify therapy."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new data add to and reinforce ibezapolstat's emerging overall distinctive product profile, particularly the favorable microbiome-related unexpected findings." He added: "Furthermore, the initial in vitro activity shown against the Bioterrorism Category A pathogen B. anthracis (Anthrax) with some of our earlier-stage compounds included a ciprofloxacin-resistant strain. Selective microbiome effects will be tested with these new compounds as they proceed through development to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other critical gram-positive pathogens in parallel with planning for the Anthrax bioterrorism program. The presentation is available on the Acurx Pharmaceuticals website www.acurxpharma.com
Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.
Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
About the C. difficile Symposium (ICDS)
The International C. difficile Symposium (ICDS) is now established as the premier venue for the review of Clostridium difficile research.
The 1st meeting was held in Kranjska Gora in 2004, the 2nd in Maribor in 2007, while all earlier meetings were in Bled in 2010, 2012, 2015 and in 2018. ICDS in 2020 was held virtually. The 2024 meeting will provide the ideal opportunity to review progress in epidemiology, diagnostics, clinical trials, basic research and in understanding C. difficile pathogenesis and controlling the devastating disease it causes.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment).
In the now completed Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment.
There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022).
In the Phase 2 clinical trial, the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP). To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com
gfp927z
6月前
>>> Acurx Pharmaceuticals, Inc. Reports Second Quarter 2024 Results and Provides Business Update
PR Newswire
Aug 9, 2024
https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-reports-second-110100900.html
STATEN ISLAND, N.Y., Aug. 9, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("we" or "Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today certain financial and operational results for the second quarter ended June 30, 2024.
Highlights of the second quarter ended June 30, 2024, or in some cases shortly thereafter, include:
In April 2024, we completed a successful End-of-Phase 2 Clinical Meeting with FDA and confirmed Phase 3 Readiness for ibezapolstat (IBZ) to enter Phase 3 clinical trials for the treatment of C. difficile infection. Agreement with FDA was reached on key elements to move forward with our international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. We've since continued activities to advance IBZ into international Phase 3 clinical trials for treatment of C. difficile Infection. In parallel, we're also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.
Also in April 2024, we attended the European Society of Microbiology and Infectious Disease (or ESCMID) scientific congress. Dr. Kevin Garey provided an oral presentation of our Phase 2 data entitled: "A Phase 2, Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of C. difficile Infection." Dr. Garey is Professor and Chair, University of Houston College of Pharmacy, and the Principal Investigator for microbiology and microbiome aspects of the IBZ clinical trial program and Acurx Scientific Advisory Board member. The oral presentation included additional analyses of clinical and microbiological data and is available on our website at www.acurxpharma.com. The complete Phase 2 results are being prepared for submission to a prominent scientific journal for publication. The oral presentation is available on our website at www.acurxpharma.com.
In May 2024, we announced that the European Medicines Agency (or EMA) approved our application to be designated as a small to medium sized enterprise (or SME) in Europe which provides for certain benefits including fee reductions and other support from the EMA for seeking a Marketing Authorization for Europe.
In July 2024, results from the IBZ Phase 2 clinical trial in patients with C. difficile Infection were presented at the 17th Biennial Congress of the Anaerobe Society of the Americas by Taryn A. Eubank, PharmD, BCIDP, Research Assistant Professor, University of Houston College of Pharmacy delivered an oral presentation entitled: "Clinical Efficacy of Ibezapolstat in CDI: Results from Phase 2 trials."
Also in July 2024, and very timely given our late-stage development progress, the USPTO (United States Patent and Trademark Office) granted Acurx a new patent for IBZ which specifically encompasses the "treatment of C. difficile infection while reducing recurrence of infection and improving the health of the gut microbiome. This patent expires in June 2042 and we think will provide an important downstream competitive advantage.
In August 2024, we submitted our request to FDA for a meeting to review our manufacturing processes and specifications for drug substance and final product and packaging (a "CMC Meeting) in order to commence Phase 3 clinical trials. This FDA submission is customary and follows our successful End of Ph2 clinical meeting with FDA which confirmed our Ph3 clinical trial readiness. We anticipate convening a meeting with FDA regarding CMC in the fourth quarter.
Throughout the rest of this year, we'll continue to roll out our Phase 2 results in either oral presentations or scientific posters (in some cases both), which will include results from new analyses as data become available, at various prominent scientific conferences including:
In September 2024, the World Antimicrobial Resistance conference in Philadelphia;
In September 2024, the 8th International C. difficile Symposium (or ICDS meeting) in Bled, Slovania, which is the premiere global venue for the review of C. difficile research; and
In October 2024, we will be presenting at the annual meeting of the Infectious Diseases Society of America (or ID Week) in Los Angeles.
International Regulatory Initiatives will continue in 2H 2024.
Second Quarter of 2024 Financial Results
Cash Position:
The Company ended the quarter with cash totaling $6.4 million, compared to $7.5 million as of December 31, 2023. During the second quarter, the Company sold an additional 133,066 shares under its ATM financing program, with gross proceeds of approximately $0.3 million.
R&D Expenses:
Research and development expenses for the three months ended June 30, 2024 were $1.8 million compared to $1.7 million for the three months ended June 30, 2023. The increase was due primarily to an increase in manufacturing related costs during the quarter of $0.4 million, partially offset by a reduction in consulting fees of $0.3 million. For the six months ended June 30, 2024 research & development expenses were $3.4 million compared to $2.8 million for the six months ended June 30, 2023, an increase of $0.6 million primarily due to $0.8 million increase in manufacturing related costs offset by $0.2 million decrease in consulting fees.
G&A Expenses:
General and administrative expenses for the three months ended June 30, 2024 were $2.3 million compared to $1.7 million for the three months ended June 30, 2023, an increase of $0.6 million. The increase was primarily due to $0.3 million increase in professional fees and $0.2 million increase in non cash share-based compensation related costs. For the six months ended June 30, 2024, general and administrative expenses were $5.1 million compared to $3.6 million for the six months ended June 30, 2023, an increase of $1.5 million. The increase was primarily due to $1.0 million increase in professional fees, $0.4 million increase in non cash share-based compensation costs and $0.1 million increase in legal costs
Net Income/Loss:
The Company reported a net loss of $4.1 million or $0.26 per diluted share for the three months ended June 30, 2024 compared to a net loss of $3.4 million or $0.28 per diluted share for the three months ended June 30, 2023, and a net loss of $8.5 million or $0.54 per share for the six months ended June 30, 2024, compared to a net loss of $6.3 million or $0.53 per share for the reasons previously mentioned.
The Company had 15,996,168 shares outstanding as of June 30, 2024.
Conference Call
As previously announced, David P. Luci, President and Chief Executive Officer, and Robert G. Shawah, Chief Financial Officer, will host a conference call to discuss the results and provide a business update as follows:
Date:
Friday, August 9, 2024
Time:
8:00 a.m. ET
Toll free (U.S. and International):
877-790-1503
Conference ID:
13747936
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate preparing to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
gfp927z
6月前
>>> USPTO Grants Acurx Pharmaceuticals New Patent for Ibezapolstat to Treat CDI While Reducing Recurrence of Infection and Improving Health of the Gut Microbiome
PR Newswire
Jul 17, 2024
https://finance.yahoo.com/news/uspto-grants-acurx-pharmaceuticals-patent-110000920.html
STATEN ISLAND, N.Y., July 17, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced that a new patent has been granted by the United States Patent and Trademark Office (USPTO) on July 16, 2024. This patent relates to ibezapolstat and its use to treat C. difficile Infection (CDI) while reducing the recurrence of the infection, as well as improving the health of the gut microbiome. This is the latest in the series of granted patents and pending patent applications that Acrux has filed to protect its proprietary technologies in the field of antimicrobials.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This patent is very important and timely as ibezapolstat continues to demonstrate previously unexpected and favorable effects on the gut microbiome while at the same time curing the C. difficile bacterial infection and preventing recurrent infection." He further added: "As we continue to prepare for initiation of our Phase 3 clinical program, we expect this feature of ibezapolstat's selective mechanism of action to be further demonstrated and to be an important competitive advantage over currently available antibiotics by reducing the recurrence of the infection. This could have a dramatically favorable effect on patient outcomes and on reducing downstream healthcare costs."
David P. Luci, President & CEO of Acurx stated: "This latest patent is part of our company's pivotal product, ibezapolstat, which is a two-dimensional antibiotic to cure infections clinically comparable to marketed antibiotics while restoring the microbiome and preventing reinfections which is unusually positive for CDI antibiotics."
Acurx has previously announced that it had a successful FDA End-of- Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also now preparing to submit requests for guidance to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. The Company's Scientific Advisory Board concurred with this recommendation.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment.
There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October 2022).
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19 and its aftermath. The Company had determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated patients who agreed to observation for up to three months following Clinical Cure of CDI experienced no recurrence of infection.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI).
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of healthcare-associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
gfp927z
8月前
>>> Q1 2024 Acurx Pharmaceuticals Inc Earnings Call
Thomson Reuters
May 15, 2024
https://finance.yahoo.com/news/q1-2024-acurx-pharmaceuticals-inc-024052823.html
Participants
David P. Luci; Co-Founder, President, CEO, Corporate Secretary & Director; Acurx Pharmaceuticals, Inc.
Robert G. Shawah; Co-Founder & CFO; Acurx Pharmaceuticals, Inc.
Robert J. DeLuccia; Co-Founder & Executive Chairman; Acurx Pharmaceuticals, Inc.
Antonio Eduardo Arce; MD of Equity Research & Senior Healthcare Analyst; H.C. Wainwright & Co, LLC, Research Division
James Francis Molloy; MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst; Alliance Global Partners, Research Division
Unidentified Participant
Presentation
Operator
Hello, and welcome to the Acurx Pharmaceuticals First Quarter 2024 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference is being recorded. It's now my pleasure to turn the conference over to CFO, Robert Shawah. Please go ahead.
Robert G. Shawah
Thank you, Kevin. Good morning, and welcome to our call. This morning we issued a press release providing financial results and company highlights for the first quarter of 2024, which is available on our website at acurxpharma.com. Joining me today is Dave Luci, President and CEO of Acurx, who will give a corporate update and outlook; as well as our Executive Chairman, Bob DeLuccia. After that, I'll provide some highlights of the financials from the quarter ended March 31, 2024, then turn the call back over to Dave and Bob for their closing remarks.
As a reminder, during today's call, we'll be making certain forward-looking statements. These forward-looking statements are based on current information, assumptions, estimates and projections about future events that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. Investors should consider these risks and other information described in our filings made with the Securities and Exchange Commission, including our quarterly report on Form 10-Q, which we filed on Tuesday, May 14, 2024.
You're cautioned not to place undue reliance on these forward-looking statements, and Acurx disclaims any obligation to update such statements anytime in the future. This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast today, May 15, 2024.
I'll now turn the call over to Dave Luci. Dave?
David P. Luci
Thanks, Rob. Good morning, everyone, and thanks for joining us to review our financial results for the first quarter and also to hear some exciting recent updates. Then we'd be pleased to take any questions. First, I'll summarize some of our key activities for the first quarter of 2024, or in some cases, shortly thereafter. In January, we announced positive comparative microbiology and microbiome data for ibezapolstat, our lead antibiotic candidate in C. diff patients from the Phase IIb clinical trial segment.
Ibezapolstat outperformed vancomycin, a standard of care, showing eradication of fecal C. difficile at day 3 of treatment in 15 of 16 treated patients, 94%, versus vancomycin, which had eradication of C. difficile in 10 of 14 treated patients or 71%. Additional data from the Phase IIb clinical trial showed ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacteria species believed to confer health benefits, including preventing recurrent C. diff infection.
Additional data from exploratory endpoints will provide further favorable separation between these 2 therapeutic options in our Phase III clinical trial program and ultimately in the marketplace, if approved. We remain particularly excited about the dual impact of ibezapolstat to treat acute C. difficile on the one hand, while appropriately managing the long-term care of each patient's microbiome, which we believe is truly exceptional for antibiotic therapy.
Having robust preclinical, clinical and manufacturing data to date, we submitted, in January, a formidable information package to the FDA, along with a request for an end of Phase II meeting, which was granted on February 26, and the meeting was convened on April 17. At the FDA meeting, we reached agreement on key elements of our Phase III program. including, importantly, agreement with the FDA regarding readiness to proceed to Phase III, as well as agreement on the regulatory pathway for a new drug application filing for marketing approval in the U.S. We will press release further details on the FDA meeting premarket this morning.
In February, we announced that the European Medicines Agency approved our application to be designated as a small to medium-sized enterprise or SME in Europe, which provides for certain benefits, including fee reductions and other support from the agency for seeking a marketing authorization in Europe. We attended the European Society of Microbiology and Infectious Disease or ESCMID Scientific Congress in April 2024, where Dr. Kevin Garey, Professor and Chair, University of Houston, College of Pharmacy, and the Principal Investigator for Microbiology and Microbiome aspects of our clinical trial program, and our Scientific Advisory Board member, provided an oral presentation of Phase II data entitled, "A Phase II Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of C. difficile Infection". The presentation included additional analyses of clinical and microbiological data and is available on our website at www.acurxpharma.com. The complete Phase II results are being prepared for submission to a prominent scientific journal for publication this year.
Throughout the rest of this year, we'll continue to roll out our Phase II results in either oral presentations or scientific posters, or in some cases both, which will include results from new analyses as data become available at various prominent scientific conferences, including the Houston C. diff & Microbiome Conference later this month, the Anaerobe Society of the Americas Annual Conference in July, the World Antimicrobial Resistance Conference in September. Also in September is the International C. diff Symposium, and of course, the Annual Meeting of the Infectious Disease Society of America, or ID Week, in October.
Throughout the first quarter, we continued preparations for Phase III trials, including advances in micro and manufacturing, CRO selection and clinical site screening, and building a team of international drug development experts to support our Phase III mandate. To ensure Phase III clinical trial enrollment as quickly as possible, we're adding substantially more clinical trial sites, way above the number used to conduct the U.S.-only Phase II trials.
We're now finalizing costs and time lines and our plan is to conduct the required 2 Phase III registration trials consecutively, not concurrently, given the size of our company, and need to use our financial resources most efficiently. The time line to conduct our Phase III trials is not a concern since ibezapolstat will have a rolling 10 years of regulatory exclusivity in the U.S. from the date of the FDA approval, with similar exclusivity available in Europe, the U.K., Japan, and Canada.
We will continue to seek a strategic transaction for the company, including a potential partnership for the further development and potential commercialization of ibezapolstat, alongside preparation for Phase III and our build-out strategy. At this time, we have no commitments to our potential partners or others to report. But now having FDA confirmation of the registration plan, this has become an active initiative.
As we've consistently reported, ibezapolstat clinical results continue to outperform in a series of potentially life-threatening infection. The CDC categorizes C. difficile as an urgent threat and calls for new classes of antibiotics for initial treatment that also have a low incidence of recurrence. Ibezapolstat is also FDA fast track designated for the treatment of C. difficile infection.
Initially, we believe ibezapolstat, if approved, could make a favorable impact by reducing the cost burden of recurrent C. diff infection on the U.S. health care system, which is estimated at $4.7 billion annually. We do believe the best is yet to come.
And now back to our CFO, Rob Shawah, to guide you through the highlights of our financial results for the first quarter. Rob?
Robert G. Shawah
Thanks, Dave. Our financial results for the first quarter ended March 31, 2024, were included in our press release issued earlier this morning. The company ended the quarter with cash totaling $8.9 million compared to $7.5 million as of December 31, 2023. During the first quarter, the company sold an additional 1,121,793 shares under its ATM financing program with gross proceeds of approximately $4.4 million.
Research and development expenses for the 3 months ended March 31, 2024, were $1.6 million compared to $1 million for the 3 months ended March 31, 2023. The increase was due primarily to an increase in manufacturing-related costs during the quarter. General and administrative expenses for the 3 months ended March 31, 2024, were $2.8 million compared to $1.9 million for the 3 months ended March 31, 2023. The increase was due primarily to a $0.7 million increase in professional fees and a $0.2 million increase in noncash share-based compensation.
The company reported a net loss of $4.4 million or $0.28 per diluted share for the 3 months ended March 31, 2024, compared to a net loss of $2.9 million or $0.25 per diluted share for the 3 months ended March 31, 2023, all for the reasons we previously mentioned. The company had 15,757,102 shares outstanding as of March 31, 2024.
With that, I'll turn the call back over to Dave. Dave?
David P. Luci
Thanks, Rob, and thanks to all of you for joining us today. I'll now ask Bob DeLuccia, our Executive Chairman, who managed the FDA post-Phase II meeting process, to provide his perspective on the FDA meeting in the company's Phase III mandate. Bob?
Robert J. DeLuccia
Yes. Thanks, Dave. So let me just add a few thoughts on top of Dave's comments about our end of Phase II meeting with the FDA. In general, it was a very thorough, productive, and successful meeting regarding 4 things.
First, we had overall agreement that was reached based upon the strength of our preclinical and Phase II clinical trial results, including the anticipated safety database, we're ready to move forward with plans for our Phase III program.
Second, with respect to the Phase III clinical trial design, as expected, it will be the same design as our Phase IIb trial, which is noninferiority to vancomycin, with the primary endpoint being clinical cure after 10 days of treatment, and a secondary endpoint of sustained clinical cure about 30 days after the end of treatment.
Third, we agreed on the statistical analysis patient population, which will be a modified intent to treat or what's called MITT population, with an estimated 450 subjects in that MITT group. And this is roughly what we had expected and will now be in sync with requirements for an EMA clinical trial authorization.
And lastly, agreement on the registration program for 2 noninferiority trials versus vancomycin, which would be required for marketing approval. Now I'd also add that we were very pleased with suggestions from the FDA, including ultimate labeling and overall supportive tone of the FDA from our submitted data to date and our plan going forward. So bottom line, we now have a complete regulatory road map to move forward with our Phase III program, which is the last clinical development step toward marketing registration of ibezapolstat globally. For a small entrepreneurial company like Acurx, this is a very significant milestone that we've reached.
And Dave, if you don't mind, I'd like to add one more thing just on top of what you said. Recall that ibezapolstat has FDA fast track designated status due to the urgent need classification by the U.S. CDC for new classes of antibiotics. And there are similar classifications like this available in other geographies, including Europe, the U.K., Japan and Canada. If approved, ibezapolstat will be the first new class of antibiotics brought to the market in over 3 decades. So we've got no time to waste to get this new product over the goal line. And with the continued support of all our shareholders, we have a clear vision and a strong passion to be successful for the ultimate benefit of patients who need better treatment for C. difficile infection and all our stakeholders and, in general, for better public health. Kevin?
Question and Answer Session
Operator
(Operator Instructions) Our first question today is coming from Ed Arce from H.C. Wainwright.
Antonio Eduardo Arce
Bob, I appreciate the comments at the end. Those were some of the questions I had regarding the specifics around the trial. A couple of follow-ups there. Firstly, the 450 patients or subjects that you mentioned, is that the total number for the trial? And also, the usual requirement from the FDA of 2 well-designed pivotal studies. I want to just confirm that the Phase Ib is being considered as one of those 2. And so this upcoming trial would be the final study?
Secondly, I wanted to ask about the costs and time lines. I know that you said that those are currently being finalized. But any preliminary or early commentary around those would be helpful for us. And then lastly, around the strategic partners and your efforts now that you characterized as being active, now that you have a pathway for a pivotal study. I'm wondering, although you don't have any current commitments, do you have any active discussions at this point? Thanks so much.
David P. Luci
Thank you for your questions, Ed. The last question being the easiest, I'll hit that 1 first. So we have several active discussions at the moment. Nothing to report. But for example, the company will be well represented at the BIO CEO conference in San Diego, and my schedule is chock full. So there's a lot of activity. We felt it most appropriate, before making outbound calls, to have the FDA piece to the puzzle in place, because we now are truly Phase III ready and that removes another piece of the puzzle in terms of things being set in stone. So that's all set.
On the first question, with regard to the 450 MITT patients, that's the total MITT patients for each of 2 Phase III registration trials. So the Phase IIb is not considered a registration trial. You may recall the small numbers of patients. And quite frankly, we needed a lot more patients to have satisfactory safety database for an NDA application thereafter. So it's 450 patients MITT for each of 2 trials, for a total of 900.
And to your question, we are still going through the cost things. So we don't know exactly how much it will cost. And in some cases, if we have a partnership, it may be that some of the work that we would have paid for would be internalized by a fully integrated pharma company that will be side-by-side with us with mutual interest to get the Phase III program done as quickly as possible, and using our Phase III data for filing in Europe, the U.K., Japan. So the MITT piece to the puzzle was a quick conversation with the FDA, because really, you need that to get to file for approval in Europe and the U.K. So by agreeing on that particular point, we were able to avoid further clinical trials beyond the 2 Phase IIIs. And quite literally, we have an equal pathway in the U.S., the U.K. and Europe. So we're kind of delighted with that piece to the puzzle. But I think that's -- is there another piece to your question that I may have missed?
Robert J. DeLuccia
Yes, Dave. Question on time line. I mean I can answer if you'd like to?
David P. Luci
Okay. Time line. Yes, we feel, based on what we spent out so far that would be 1.5 years to 2 years from first patient enrolled.
Robert J. DeLuccia
And Ed, this is Bob. Just to reiterate, too, the 2 Phase III trials are straightforward from the FDA guidelines, October 22, I think it was, guidelines. And that's a very clear path for what's needed for approval and an NDA.
Operator
(Operator Instructions) Your next question is coming from Mike Boyd, a private investor.
Unidentified Participant
Thank you for the update. It's very exciting, and I can't wait to see the next steps. I had a quick question, easy one I hope. Has the company considered a priority review voucher for this application?
David P. Luci
Thanks for the question, Mike. Bob, do you want to hit that one?
Robert J. DeLuccia
Yes. I mean we already have priority review because of our FDA fast track status. So we already have that.
Unidentified Participant
Yes. But the voucher itself is actually -- there's value to that. You could actually sell that if you chose. Current market value is about $100 million. So looking at that as a source of possible funding at some point.
Robert J. DeLuccia
We could certainly take a look.
Unidentified Participant
Okay. Cool. I mean the timing is right to begin thinking about it. It's associated with the NDA. So it's time to put it on the radar if it's something that the FDA would consider.
David P. Luci
Okay.
Operator
Your next question today is coming from James Molloy from Alliance Global Partners.
James Francis Molloy
Guys, I apologize if I missed it on the call. Did you guys state when you anticipate starting the first of the 2 Phase IIIs? And can you walk us through what the all-in cost on the Phase IIIs are anticipated?
David P. Luci
Thanks, Jim, and good morning. We hope to start -- we will be ready to start in the fourth quarter of this year with enrollment with our manufacturing update that we recently received. So we hope to be funded satisfactorily by then in order to start. So that's the gating factor. But yes, we hope to start in the fourth quarter, and then enrollment should take 18 to 24 months. And it's difficult for us to guesstimate exactly how much this is going to cost, because we have a lot of partnering discussions currently ongoing and they're all different. And they all have various internal capabilities that dramatically impact what the Phase III mandate will cost. It's certainly something in the $50 million to $60 million range if we were to do it all independently ourselves. So a partnership would be an appropriate course.
James Francis Molloy
How would you characterize the current partnership environment? And obviously, after Phase III, it's your best deal, you're obviously not there. But how do you characterize sort of going into Phase III, the partnership opportunities you're seeing?
David P. Luci
I would characterize it as pretty robust. I mean, probably my last 20 e-mails in my inbox are people wanting to meet me, and I haven't even looked at the e-mails yet. That's just from overnight. I mean, it's just a lot of interest, and we may not be enrolling in Phase III, but we're Phase III ready. And we know we have a drug from our Phase IIb data. So we have to be patient and we have to take the right deal.
And when things come along that are going to constitute 60% of the company being lost to a round of investment, then sometimes it's the deals that you don't do that make the most sense. So we're trying to be judicious about raising capital as nondilutively as possible, knowing that we have a drug, and we're Phase III ready. And there aren't a lot of Phase III antibiotics out there right now, especially not in a $1 billion-plus market, where you have a reasonable chance to be frontline therapy.
James Francis Molloy
Maybe last questions on my end. On the design, I know that, obviously, 1 year, 1.5 years to get to run the first of the Phase IIIs. Is there an opportunity for any interim looks and any thoughts on timing on that? And then any update on the PASTEUR Act? What's going on?
David P. Luci
Yes, I'll leave that -- the question on the PASTEUR Act, I'll leave to Bob. There's some new legislation -- actually old legislation that may be expanded to include antibiotics that treat life-threatening infections that Katie Britt in the Senate has gotten in touch with the Health and Human Services about, but I'll let Bob talk about that.
But the interim look thing, that's kind of like a head fake. I know it's NBA playoff time. So for you NBA fans, the interim look, that would go through an independent committee of scientists and doctors. And if you take an interim look, you necessarily statistically have to add patients to the trial. And the interim look doesn't give you any sense of, percentage-wise, how you're doing with the primary endpoint or secondary endpoints. All it does is this group of experts tell you to either keep going or to stop due to futility. So for the amount of information you get out of that, to me, is not worth adding millions of dollars in time to a trial.
Robert J. DeLuccia
Yes. I agree with you, Dave, on that, for sure. And I hope that answers the question. But remember, this is a blinded trial. So you really can't break the blind. You've got to continue to proceed. I think there was a second question here regarding...
David P. Luci
It was about PASTEUR Act.
Robert J. DeLuccia
What was the question?
David P. Luci
What's going on with the PASTEUR Act?
Robert J. DeLuccia
Yes, PASTEUR Act. There's a lot of effort to try to get that through. Really unlikely going to occur this year under the current political environment. However, there is some activity with a special program that requires a drug to be determined as a material threat in order to get some additional funding from a government organization called BARDA for new classes of antibiotics that are in late-stage clinical trials, namely Phase III.
So this is being circulated as pending legislation, trying to move it forward this year. I wouldn't put a high probability that it's going to get through this year. But if it does, we'll be able to tap into that for some partial funding for our Phase III program.
David P. Luci
Actually, just a slight nuance on that is that the legislation is actually old. It's been approved a long time ago. So what needs to happen is that the scope of the program would need to be expanded, which I understand can be done by HHS on their own. It would need to be expanded to include antimicrobials that treat life-threatening infections. So it doesn't rise to the level of needing a new law, the law is there, it's just the program needs to be expanded to include this new class of things that ultimately would be stockpiled by the Federal government through the Department of Defense.
Operator
We've reached the end of our question-and-answer session. I'd like to turn the floor back over for any further or closing comments.
David P. Luci
We'd just like to thank everyone for participating today, and thank you for your patience and the best is yet to come.
Operator
Thank you. That does conclude today's teleconference. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.
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gfp927z
8月前
>>> Acurx Pharmaceuticals Inc (ACXP) Q1 2024 Earnings Call Transcript Highlights: Key Financial and ...
GuruFocus Research
May 16, 2024
https://finance.yahoo.com/news/acurx-pharmaceuticals-inc-acxp-q1-070055271.html
Cash Position: $8.9 million as of March 31, 2024, up from $7.5 million as of December 31, 2023.
Net Loss: $4.4 million or $0.28 per diluted share for Q1 2024, compared to a net loss of $2.9 million or $0.25 per diluted share for Q1 2023.
Research and Development Expenses: $1.6 million for Q1 2024, up from $1 million for Q1 2023.
General and Administrative Expenses: $2.8 million for Q1 2024, up from $1.9 million for Q1 2023.
Shares Outstanding: 15,757,102 as of March 31, 2024.
ATM Financing: Sold an additional 1,121,793 shares with gross proceeds of approximately $4.4 million during Q1 2024.
Release Date: May 15, 2024
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
Positive Points
Ibezapolstat showed superior efficacy in eradicating C. difficile compared to vancomycin in Phase IIb trials, with a 94% success rate versus 71% for vancomycin.
Ibezapolstat has demonstrated the ability to preserve and allow regrowth of key gut bacteria, potentially reducing the recurrence of C. diff infections.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) has successfully reached agreement with the FDA on key elements of the Phase III program, indicating readiness to proceed to the next phase of clinical trials.
The company has secured SME status in Europe, providing benefits such as fee reductions and support from the European Medicines Agency.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) has a robust financial position with an increase in cash from $7.5 million to $8.9 million and successful additional share sales generating $4.4 million.
Negative Points
The company reported an increased net loss of $4.4 million for Q1 2024, up from $2.9 million in the same period the previous year.
Research and development expenses increased significantly, from $1 million to $1.6 million, due to higher manufacturing-related costs.
General and administrative expenses also rose from $1.9 million to $2.8 million, driven by increases in professional fees and noncash share-based compensation.
Acurx Pharmaceuticals Inc (NASDAQ:ACXP) is still in the process of finalizing costs and timelines for Phase III trials, indicating potential uncertainties in future expenditures.
The company has not yet secured any commitments from potential partners for further development and commercialization of ibezapolstat, despite active discussions.
Q & A Highlights
Q: Bob, can you confirm the total number of subjects for the upcoming trial and clarify if the Phase IIb is considered one of the two pivotal studies required by the FDA? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - The total number of subjects for each of the two Phase III registration trials is 450, making it 900 in total. The Phase IIb is not considered a registration trial due to its small size. The upcoming trials are necessary to build a satisfactory safety database for an NDA application.
Q: Could you provide any preliminary information on the costs and timelines for the upcoming trials? Also, are there any active discussions regarding strategic partnerships? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We are currently finalizing the costs and timelines. Discussions about partnerships are active, especially now that we have a clear pathway for a pivotal study. We are engaging in several discussions, but nothing is finalized yet.
Q: When do you anticipate starting the first of the two Phase III trials? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We aim to start enrollment in the fourth quarter of this year, contingent on adequate funding. The enrollment is expected to take 18 to 24 months.
Q: Has the company considered applying for a priority review voucher for this application? A: Robert J. DeLuccia - Co-Founder & Executive Chairman, Acurx Pharmaceuticals, Inc. - We already have priority review due to our FDA fast track status. However, we are open to exploring the possibility of a priority review voucher, which could be a significant source of funding.
Q: Can you discuss the partnership environment as you approach Phase III? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - The environment is quite robust. We have a lot of interest from potential partners, and we are being judicious in our discussions to ensure we make the right deal without overly diluting our company.
Q: Is there an opportunity for any interim looks during the Phase III trials, and could you update us on the PASTEUR Act? A: David P. Luci - Co-Founder, President, CEO, Corporate Secretary & Director, Acurx Pharmaceuticals, Inc. - We do not plan to conduct interim looks as they require adding patients and do not provide significant insights. Regarding the PASTEUR Act, it is unlikely to pass this year, but we are monitoring potential funding opportunities for new classes of antibiotics through other government programs.
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
gfp927z
1年前
>>> Acurx Announces Positive Comparative Microbiology and Microbiome Data for Ibezapolstat from Phase 2b Clinical Trial in CDI Patients
Yahoo Finance
January 17, 2024
https://finance.yahoo.com/news/acurx-announces-positive-comparative-microbiology-120100113.html
Ibezapolstat outperformed vancomycin showing eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 treated patients (94%), versus vancomycin which had eradication of C. difficile in 10 of 14 treated patients (71%).
Ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent recurrence of CDI
Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days
Preparation underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Jan. 17, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced positive comparative microbiology and microbiome data for ibezapolstat, its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. Data showed that ibezapolstat outperformed vancomycin, a standard of care to treat patients with CDI, with eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 patients (94%) versus vancomycin which had eradication of fecal C. difficile in 10 of 14 patients (71%). In addition, ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent CDI recurrence. Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days. Preparation is underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials.
The Company also announced that a scientific poster will be presented on January 18, 2023 at the Gulf Coast Consortia Antimicrobial Resistance (AMR) Conference in Houston, Texas by Kevin Garey, PharmD, MS, Professor and Chair, University of Houston College of Pharmacy, the Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member. The poster will show comparative data details from the Phase 2b clinical trial entitled: "A Phase 2, Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides difficile Infection."
After the presentation, the poster will be posted on Acurx website: www.acurxpharma.com
According to Dr. Garey: "These results help validate our ongoing scientific investigations into the anti-CDI recurrence effects of ibezapolstat. Our microbiologic findings show that markedly fewer patients treated with ibezapolstat had persistent C. difficile compared to patients treated with vancomycin. He further stated: "Preservation of key health-conferring native gut bacteria, such as Firmicutes, in patients treated with ibezapolstat has now been shown consistently during all clinical studies. These results correlate with prior findings by showing superior preservation of key native gut bacteria compared to vancomycin in CDI patients. Preservation of native gut bacteria during treatment for CDI is believed to be a key component for preventing recurrence of CDI. These findings will need to be further validated in the phase 3 studies but the results to date support the importance of this new class of antibiotics with a novel mechanism of action that does not target native gut bacteria."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new comparative data are very important and timely to enhance our data package for an end of Phase 2 FDA Meeting which is targeted for second quarter this year. He further stated: "Parallel preparations continue on schedule for Phase 3 clinical trials start up later this year, including timely availability of clinical trial supply.
David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate that favorable differentiation between the two therapeutic options will continue to be shown in Q1 2024 including extended clinical cure and additional microbiome comparison data. We expect to leverage this success in a $1 billion plus US CDI global market as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also anticipates its price point for ibezapolstat, if approved, could meet or beat other antibiotics recommended for use in treating patients with CDI, thereby providing the whole package of clinical comparability with microbiome health, safety and cost for patients with this life-threatening disease."
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti- recurrence microbiome properties seen in the Phase 2a trial, including the treatment- related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. The Company's Scientific Advisory Board concurred with this recommendation.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October, 2022).
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19 and its aftermath. The Company had determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
tw0122
1年前
ACXP good diarrhea trials .. Acurx Announces Positive Comparative Microbiology and Microbiome Data for Ibezapolstat from Phase 2b Clinical Trial in CDI Patients
Source: PR Newswire (US)
Ibezapolstat outperformed vancomycin showing eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 treated patients (94%), versus vancomycin which had eradication of C. difficile in 10 of 14 treated patients (71%).
Ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent recurrence of CDI
Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days
Preparation underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Jan. 17, 2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced positive comparative microbiology and microbiome data for ibezapolstat, its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. Data showed that ibezapolstat outperformed vancomycin, a standard of care to treat patients with CDI, with eradication of fecal C. difficile at Day 3 of treatment in 15 of 16 patients (94%) versus vancomycin which had eradication of fecal C. difficile in 10 of 14 patients (71%). In addition, ibezapolstat, but not vancomycin, consistently preserved and allowed regrowth of key gut bacterial species believed to confer health benefits including to prevent CDI recurrence. Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days. Preparation is underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials.
The Company also announced that a scientific poster will be presented on January 18, 2023 at the Gulf Coast Consortia Antimicrobial Resistance (AMR) Conference in Houston, Texas by Kevin Garey, PharmD, MS, Professor and Chair, University of Houston College of Pharmacy, the Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member. The poster will show comparative data details from the Phase 2b clinical trial entitled: "A Phase 2, Randomized, Double-Blind Study of Ibezapolstat Compared with Vancomycin for the Treatment of Clostridioides difficile Infection."
After the presentation, the poster will be posted on Acurx website: www.acurxpharma.com
According to Dr. Garey: "These results help validate our ongoing scientific investigations into the anti-CDI recurrence effects of ibezapolstat. Our microbiologic findings show that markedly fewer patients treated with ibezapolstat had persistent C. difficile compared to patients treated with vancomycin. He further stated: "Preservation of key health-conferring native gut bacteria, such as Firmicutes, in patients treated with ibezapolstat has now been shown consistently during all clinical studies. These results correlate with prior findings by showing superior preservation of key native gut bacteria compared to vancomycin in CDI patients. Preservation of native gut bacteria during treatment for CDI is believed to be a key component for preventing recurrence of CDI. These findings will need to be further validated in the phase 3 studies but the results to date support the importance of this new class of antibiotics with a novel mechanism of action that does not target native gut bacteria."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new comparative data are very important and timely to enhance our data package for an end of Phase 2 FDA Meeting which is targeted for second quarter this year. He further stated: "Parallel preparations continue on schedule for Phase 3 clinical trials start up later this year, including timely availability of clinical trial supply.
David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate that favorable differentiation between the two therapeutic options will continue to be shown in Q1 2024 including extended clinical cure and additional microbiome comparison data. We expect to leverage this success in a $1 billion plus US CDI global market as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also anticipates its price point for ibezapolstat, if approved, could meet or beat other antibiotics recommended for use in treating patients with CDI, thereby providing the whole package of clinical comparability with microbiome health, safety and cost for patients with this life-threatening disease."
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti- recurrence microbiome properties seen in the Phase 2a trial, including the treatment- related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. The Company's Scientific Advisory Board concurred with this recommendation.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October, 2022).
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19 and its aftermath. The Company had determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
gfp927z
1年前
>>> Acurx Announces Positive Phase 2b Results Showing 100% of Patients Who Had Clinical Cure with Ibezapolstat Also Had Sustained Clinical Cure
PR Newswire
December 11, 2023
https://finance.yahoo.com/news/acurx-announces-positive-phase-2b-120100375.html
All 15 ibezapolstat-treated patients in Phase 2b who achieved Clinical Cure (CC) at end of treatment (EOT) remained free of C. difficile Infection (CDI) recurrence through one month after EOT, for a Sustained Clinical Cure (SCC) rate of 100%
2 of 14 patients treated with standard of care, oral vancomycin, experienced recurrent infection within one month after EOT for a SCC of 86%
100% of the 25 ibezapolstat-treated patients in Phase 2 (Phase 2a and 2b) who had CC at EOT remained cured through one month after EOT
Further analyses will be forthcoming Q1 2024, as data become available, regarding other endpoints, from the Phase 2b trial, including Extended Clinical Cure (ECC) data up to 94 days and comparative effects vs vancomycin on the gut microbiome
Preparation underway for meetings with FDA, European Medicines Agency and other global regulatory agencies and advancement to international Phase 3 clinical trials
STATEN ISLAND, N.Y., Dec. 11, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections, today announced positive Phase 2b results showing 100% of CDI patients who had CC with ibezapolstat, the company's late-stage antibiotic candidate, also had SCC.
The efficacy results from the Phase 2 trial (Phase 2a and Phase 2b) are summarized in the table below:
Clinical Cure
(CC)
at EOT
Sustained Clinical Cure
(SCC)
One Month After EOT for
all evaluable patients
Sustained
Clinical Cure* (SCC) One
Month After EOT
ibezapolstat Phase 2a
10/10 (100%)
10/10 (100%)
10/10 (100%)
ibezapolstat Phase 2b
15/16 (94%)
15/16 (94%)
15/15 (100%)
ibezapolstat Phase 2a +
Phase 2b Combined
25/26 (96%)
25/26 (96%)
25/25 (100%)
vancomycin
14/14 (100%)
12/14 (86%)
12/14 (86%)
*Sustained Clinical Cure was evaluated only for patients who were CC at EOT.
Kevin Garey, PharmD, MS, Professor and Chair, University of Houston College of Pharmacy, the Principal Investigator for microbiome aspects of the ibezapolstat clinical trial program and Acurx Scientific Advisory Board member stated: "These results help validate our ongoing scientific investigations into the anti-CDI recurrence properties of ibezapolstat including maintenance and regrowth of healthy gut microbes and bile acid homeostasis. I'm excited about our ongoing investigations into a new scientific paradigm optimizing C. difficile antibiotic development to effectively cure CDI and prevent recurrence."
According to Stuart Johnson, MD, Professor of Medicine, Loyola University (Infectious Disease) and Acurx Scientific Advisory Board member: "Treatment of CDI remains an important unmet medical need, for 2 reasons. First, the potential for development of resistance in C. difficile to currently available drugs like vancomycin threatens our standard therapeutic approach. Second, recurrent disease is a very serious problem with limited available treatment options. Although vancomycin is still an effective treatment, CDI patients treated with oral vancomycin experience a recurrence rate of 18-23%. Ibezapolstat, by virtue of its novel mechanism of action, lack of cross-resistance with any marketed antibiotics, narrow antibacterial spectrum, and selective effects on the gut microbiome, appears to be a promising potential new addition to our therapeutic armamentarium. I continue to be encouraged by the accumulating data showing that ibezapolstat is clinically comparable to vancomycin in treating CDI and preventing recurrence."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "The overall Phase 2 data demonstrate a high clinical cure rate of 96% together with this 100% recurrence-free rate is a promising one-two punch to C. difficile infection for a potential front-line treatment option for patients with CDI." He further stated: "These two clinical trial endpoints, together with the Phase 1 and Phase 2a clinical trial data and with additional data analyses to come, will form the basis for a comprehensive, solid data package to present to global regulatory authorities to support advancement to Phase 3 clinical trials during the second half next year and move one step closer on its pathway to commercialization."
David P. Luci, President & CEO of Acurx, stated: "Ibezapolstat continues to demonstrate success compared to a standard of care, oral vancomycin, to treat patients with CDI. We anticipate favorable separation between the two therapeutic options will continue in Q1 2024 with extended clinical cure and microbiome comparison data. We expect to leverage this success in a $1 billion plus US CDI market internationally as we move forward with an international Phase 3 clinical trial mandate." He added: "The Company also announced its "Made in America" policy initiative for manufacture of ibezapolstat capsules for Phase 3 clinical trials and commercial supply to ensure patients have uninterrupted access to this potentially life-saving antibiotic mitigating potential supply chain disruptions."
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI
including pharmacokinetics and microbiome changes from baseline and continue to test for anti- recurrence microbiome properties seen in the Phase 2a trial, including the treatment- related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment. The Company's Scientific Advisory Board concurred with this recommendation.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Ibezapolstat was well-tolerated, with three patients each experiencing one mild adverse event assessed by the blinded investigator to be drug-related. All three events were gastrointestinal in nature and resolved without treatment. There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the historical vancomycin cure rate of approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in accordance with the applicable FDA Guidance for Industry (October, 2022).
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19 and its aftermath. The Company had determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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gfp927z
1年前
Pasteur Act -- >>> Bennet, Young, Bipartisan House Colleagues Reintroduce Bipartisan PASTEUR Act to Fight Antimicrobial Resistance
April 27, 2023
https://www.bennet.senate.gov/public/index.cfm/2023/4/bennet-young-bipartisan-house-colleagues-reintroduce-bipartisan-pasteur-act-to-fight-antimicrobial-resistance
Bipartisan, Bicameral Legislation Would Support Development of Innovative Antibiotics to Treat Resistant Infections and Improve Appropriate Antibiotic Use
Washington, D.C. — Today, Colorado U.S. Senator Michael Bennet and U.S. Senator Todd Young (R-Ind.), alongside U.S. Representatives Scott Peters (D-Calif.), Drew Ferguson (R-Ga.), Mike Levin (D-Calif.), and Jake LaTurner (R-Kan.) reintroduced the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act to encourage innovative drug development targeting the most threatening infections, improve the appropriate use of antibiotics, and ensure domestic availability of antibiotics when needed.
“Right now, we don’t have the tools to address the threat posed by antimicrobial resistance – and infectious disease experts are warning us that it will only get worse,” said Bennet. “The bipartisan PASTEUR Act is the strongest bill ever written to strengthen antibiotic development and use. It will fix our market failures, expand the pipeline for next generation antibiotics, and save lives. We can’t sit on our hands as this public health crisis arrives – we have to act now.”
“Americans understand that we must take every reasonable and responsible measure to prevent future public health crises. Antimicrobial resistance has become a growing crisis in recent years. Market failures have resulted in a lack of needed research and development in this field which is a threat to public health. Our bill would incentivize the development of new innovative antibiotics and focus on educating health care providers on how to avoid overuse or misuse of these life-saving medications in order to slow the emergence of antibiotic-resistant pathogens,” said Young.
“Antimicrobial resistance poses a growing and significant threat to Americans’ health,” said Peters. “The PASTEUR Act will help us develop better antibiotics to counter resistant infections and help doctors ensure these drugs are used responsibly to stop the emergence of new superbugs. In the wake of the COVID-19 pandemic, we must do everything in our power to prevent the next public health crisis.”
“Antibiotics make modern medicine possible and the U.S. is at risk of losing these critical drugs. Antibiotic resistant infections are becoming more commonplace, and Congress must take action so that the foundation of modern medicine doesn’t crumble,” said Ferguson. “The PASTEUR Act brings together the public and private sectors to address these drug development market failures, increase public health preparedness, and help usher in a new era of antibiotic development. This essential legislation will also improve appropriate antibiotic use across the healthcare system while enhancing and safeguarding new antibiotic development. Simply put, we must act now to keep research and development from falling behind.”
“Each year in the United States, at least 2.8 million people become infected with pathogens that are resistant to treatment and for which advanced antimicrobials are needed. Unfortunately, as the COVID-19 pandemic made clear, our country needs stronger resources to develop those antimicrobials and prevent another global pandemic,” said Levin. “Our PASTEUR ACT empowers the Department of Health and Human Services to seek expertise on the development of antimicrobials and devise a plan to make them widely available. I thank Sen. Bennet and Rep. Ferguson for leading this bicameral, bipartisan legislation and look forward to it moving through the legislative process.”
“The COVID-19 pandemic reminded us how crucial it is for our nation to continue investing in healthcare research to prevent future public health emergencies,” said LaTurner. “America can't afford to be asleep at the wheel when it comes to the threat of antimicrobial resistance. That's why I'm proud to join my colleagues in introducing the bipartisan PASTEUR Act to bolster new antibiotic development and help medical professionals prevent the overuse of lifesaving drugs.”
According to the Centers for Disease Control and Prevention’s (CDC) Antibiotic Resistance Threats in the United States report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, and at least 35,000 people die as a result. In March 2015, the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria directed federal agencies to accelerate a coordinated, full government response to antibiotic resistance and take action to expand the ability of our health care system to prevent, identify, and respond to the infection pandemic threat posed by antimicrobial resistance. Part of this plan was to increase and incent development of innovative antimicrobial drugs to treat resistant infections. Because of severe market failures in the health care system, many of the innovative antibiotic companies doing this work have filed for bankruptcy and stopped producing their critical drugs completely.
The PASTEUR Act would address this market failure and increase public health preparedness by keeping novel antibiotics on the market and improving appropriate use across the health care system. While current contracts between the government and drug makers base payment on volume, the PASTEUR Act would establish a subscription-style model which would offer antibiotic developers an upfront payment in exchange for access to their antibiotics, encouraging innovation and ensuring our health care system is prepared to treat resistant infections.
Statements of Support
“Millions will continue to die from resistant bacteria because we are out of treatment options. Antibiotics aren't working any more for most people who contract a superbug. The science is extraordinary, it's the business model that's broken. We desperately need a new way to pay for these drugs - antibiotics, antifungals, and phage therapy. The Pasteur Act is that rare, bipartisan idea that solves an incredible problem for an affordable price,” said Professor Kevin Outterson, Boston University.
“Antibiotics play a vital role in modern medicine, and we know that preserving access to these drugs is essential to any pandemic or public health emergency response. Yet the medicines that the U.S. relies on to treat serious infections have remained largely the same for nearly 40 years and are increasingly ineffective against quickly evolving bacteria. In 2023, the U.S. has already experienced several alarming antibiotic-resistant threats—and the emergence of new superbugs will continue and will only get worse. The bipartisan PASTEUR Act has the support of a diverse group of more than 230 public health and health care organizations, because it will help us fix the broken antibiotic drug pipeline and deliver important new therapies to physicians and the patients who need them. Reintroduction of the bill is an encouraging sign that policymakers remain committed to ensuring that lifesaving antibiotics are available when Americans need them most,” said David Hyun, director of The Pew Charitable Trusts’ Antibiotic Resistance Project.
"The need for legislative solutions to address the public health challenges posed by antimicrobial resistance (AMR) has been mounting for quite some time now, and we applaud the sponsors of the PASTEUR Act for their leadership. This bill will make new novel antibiotics a reality for patients and providers and fortify our healthcare system for future generations. AMR impacts us all and protection against the increasing threats of infection is not a partisan issue. We encourage broad support and quick passage of the PASTEUR Act,” said Candace DeMatteis, Vice President of Policy, Partnership to Fight Infectious Disease.
"For decades, we have seen antimicrobial resistance (AMR) soar around the world, while the pipeline for new treatments slows to a trickle due to the broken ecosystem for antimicrobial innovation. The PASTEUR Act is an integral solution to addressing the global public health crisis of AMR. The bipartisan bill will help repair the foundational challenges of the antimicrobial marketplace and drive the development of new, innovative treatments for patients,” said Rachel King, Interim President and CEO of the Biotechnology Innovation Organization.
“Infectious diseases physicians see firsthand the devastating impact of antimicrobial-resistant infections on our patients. We urgently need novel antimicrobials and investments in antimicrobial stewardship to preserve the efficacy of these precious drugs and optimize patient outcomes. The PASTEUR Act will deliver the tools we need to protect modern medicine and strengthen our preparedness for future emergencies,” said Carlos del Rio, MD, FIDSA, President, Infectious Diseases Society of America; and Interim Dean, Emory University School of Medicine.
“For people living with cystic fibrosis, difficult-to-treat infections are an unfortunate but common occurrence, and the fear of not having enough treatment options is an all too familiar concern. There is an urgent need to pass the PASTEUR Act to help ensure availability of novel antibiotics, not only for the CF community today, but for patients everywhere who could face a public health crisis tomorrow if Congress refuses to take action now,” said Mary Dwight, Senior Vice President and Chief Policy and Advocacy Officer, Cystic Fibrosis Foundation.
“Patients with drug resistant diseases are defenseless without new treatments, many of us are fighting rare diseases and we desperately need the treatments supported by the PASTEUR Act. PASTEUR is a bill for patients, and without it, too many of us will not survive our fight and those that do are facing a reduced quality of life. The new treatments created through the PASTEUR Act could one day cure me and others fighting disease with limited or no treatment options. Until then, I wake up every day hoping the medications available do not fail me again,” said Rob Purdie, Cofounder, MyCARE (MyCology Advocacy, Research & Education).
Specifically, the PASTEUR Act would:
Establish a subscription model to encourage innovative antimicrobial drug development aimed at treating drug-resistant infections. This model will be fully delinked, meaning that participating developers would not receive income, as a part of their subscription payments, based on volume or quantity of sales.
Subscription contracts would contain terms and conditions including product availability to individuals on a government health insurance plan, supporting appropriate use, and completion of postmarketing studies. These contracts could be valued between $750 million and $3 billion.
Build on existing frameworks to improve usage of the CDC National Healthcare Safety Network, the Emerging Infections Program, and other programs to collect and report on antibiotic use and resistance data.
Include transition measures such as smaller subscription contracts to support novel antimicrobial drug developers that need a financial lifeline.
Form a Committee on Critical Need Antimicrobials, consisting of representatives from federal agencies, doctors, patients, and outside experts, to develop and implement necessary guidance regarding infections of concern, and the favored characteristics of potential treatments.
Bennet and Young first introduced the PASTEUR Act in September 2020.
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gfp927z
1年前
>>> Acurx Announces Ibezapolstat Scientific Posters and Presentations at ClostPath 2023 and IDWeek 2023 Scientific Conferences
PR Newswire
October 19, 2023
https://finance.yahoo.com/news/acurx-announces-ibezapolstat-scientific-posters-110100090.html
Three scientific posters highlighting novel anti-virulence pharmacologic properties of oral ibezapolstat for C. difficile Infection; effects on toxin production, biofilm and the gut microbiome
A podium presentation entitled First of a New Class of Antibiotics (pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens; Preparing for the Next Pandemic: Antimicrobial Resistance in Gram-positive Bacterial Infections
Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
STATEN ISLAND, N.Y., Oct. 19, 2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, today announced three scientific posters were presented during the 13th International Conference on Molecular Biology and Pathogenesis of Clostridia (ClostPath) held in Banff, Canada from September 19 to 23, 2023. Additionally, two podium presentations were made at the Infectious Disease Society of America (IDSA) IDWeek™ 2023 Conference held October 11-15, 2023 in Boston, MA. Highlights of each are shown below.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "In light of our recent decision to discontinue the Phase 2b ibezapolstat clinical trial earlier than planned and prepare for Phase 3 clinical trials, the new information contained in these scientific posters and presentations at these conferences will add to our evidence-based briefing package for an End of Phase 2 FDA meeting planned for in the first half of next year." He also added: "We are currently compiling and verifying all data from the Phase 2b trial and we will report topline clinical efficacy for the primary clinical endpoint and safety data in the coming weeks, with other outcome data available later this year".
ClostPath:
Ibezapolstat modulates Clostridioides difficile virulence factors in vitro
Presented by Eugenie Basseres, et al; University of Houston College of Pharmacy
Ibezapolstat reduces toxin production by C. difficile
C. difficile In Vitro Biofilm Studies of Ibezapolstat And Comparator Antibiotics
Presented by M. Jahangir Alam et al; University of Houston College of Pharmacy
Ibezapolstat was as effective as the currently-used anti-C. difficile agents fidaxomicin, vancomycin and metronidazole to reduce biofilm-embedded C. difficile quantity and biofilm biomass
Metagenomic Evaluation of Ibezapolstat Compared to Other Anti-Clostridioides difficile Agents
Presented by Jinhee Jo, University of Houston College of Pharmacy
Ibezapolstat and fidaxomicin caused proportional increases in Bacteroidetes distinct from vancomycin and metronidazole, which caused proportional increases in Proteobacteria
IDWeek:
First of a New Class of Antibiotics (pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens
Presented by Michael Silverman, MD, FACP, Acurx's Medical Director; at the New Antimicrobials in the Pipeline session
Among the promising data for ibezapolstat in the treatment of C. difficile are in vitro potency, anti-virulence activities, high human fecal concentrations, 100% Clinical Cure rate in a 10-patient open-label trial, favorable safety profile to date, and potentially beneficial effects on the gut microbiome
Elucidating the Gram-Positive Selective Spectrum Activity of Ibezapolstat; Secondary Analysis from the Phase 2a trial; Presented by Kevin Garey, PharmD, MS, Professor& Chair, University of Houston, School of Pharmacy
Ibezapolstat showed variable selectivity against Firmicutes helping to elucidate its narrow spectrum of activity against certain pathogenic Firmicutes including C. difficile
The posters and presentations are available on the Company's website www.acurxpharma.com.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being developed as a Gram-Positive Selective Spectrum (GPSS™) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In January 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial (see https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment), the Trial Oversight Committee assessed the safety and tolerability and made its recommendation regarding early termination of the Phase 2a study and advancement to the Ph2b segment.
The Phase 2b clinical trial segment has been discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19. The Company has determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee will not be required to perform an interim analysis of this Phase 2b trial data as originally planned. Acurx will analyze the data and report topline efficacy results promptly. The Company anticipates that this decision will allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
In the now completed Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind.
This Phase 2 clinical trial will also evaluate pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. In the event noninferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin.
About ClostPath
The ClostPath conferences, which began in 1995, have been a leading venue to bring together top scientists and clinicians studying the molecular biology of clostridia and their role in health and disease. The scientific program of ClostPath 13 included lectures by internationally recognized leaders in clostridial research and clinical practice. In addition to state-of-the-art invited talks on the most recent and exciting discoveries in the field, short oral contributions were selected from submitted abstracts. Poster presentations gave attendees the opportunity to discuss their ongoing work with a broad audience in line with the goal to bring together basic science with clinical and translational research issues.
About the IDSA and IDWeek
The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). Over 9,500 participants attended this conference in October 2022.
About Clostridioides difficile Infection (CDI). According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate of two of the three antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.
About the Microbiome in Clostridioides difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa.
Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported. (CID, 2022)
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing new antibiotics for difficult to treat infections. The Company's approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and drug-resistant Streptococcus pneumoniae (DRSP).
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