- Findings from the extended LIBERTY studies and associated
post-hoc analysis support the long-term efficacy and safety
of ZYMFENTRA™, the first and only FDA-approved subcutaneous
infliximab[1],[2]
- Data from a post-hoc analysis of the LIBERTY-CD study showed
that, despite affecting drug levels, anti-drug antibodies (ADAs)
status appeared to have no significant impact on W54 clinical
outcomes or discontinuation
rates [3]
JERSEY
CITY, N.J., May 21, 2024
/PRNewswire/ -- Celltrion USA
announced today positive two-year results from the extended LIBERTY
studies (LIBERTY-CD and LIBERTY-UC) for ZYMFENTRA™
(infliximab-dyyb) in adult patients with moderately to
severely active Crohn's disease (CD) and ulcerative colitis (UC)
after induction with intravenous (IV) infliximab, further
supporting the efficacy and safety seen in previous pivotal
studies. The data was shared during 18 oral and poster
presentations at the Digestive Disease Week® (DDW) 2024
Annual Meeting in Washington,
D.C., from May 18 to
21.
The presentations included results of the two-year LIBERTY
studies and a post-hoc analysis of the LIBERTY-CD study, which
evaluated the impact of anti-drug antibodies (ADAs) on drug levels
and efficacy in patients treated with ZYMFENTRA.
"Establishing the long-term efficacy and safety profile of
ZYMFENTRA is an important step as we work to bring relief and
remission to the millions of people worldwide living with Crohn's
disease and ulcerative colitis," said Thomas Nusbickel, Chief Commercial Officer at
Celltrion USA. "These studies
reaffirm efficacy and tolerance of ZYMFENTRA as maintenance therapy
and underscore Celltrion USA's
commitment to delivering different treatment options for patients
in the gastroenterology space."
Two-year extension phase of LIBERTY studies
The extension phase of the LIBERTY studies (LIBERTY-CD and
LIBERTY-UC) was carried out over a duration of 102 weeks (including
10 weeks of infliximab IV induction), expanding upon the initial
LIBERTY trials. These two-year studies evaluated the long-term
efficacy and safety of infliximab SC in patients diagnosed with
Crohn's disease (CD) and ulcerative colitis (UC). In both
LIBERTY-CD and UC studies, efficacy results, including but not
limited to clinical remission, clinical response and
corticosteroid-free remission, were generally well maintained at
Week 102 compared to those of Week 54.
Post-hoc analysis of LIBERTY-CD study
A post-hoc analysis evaluated the impact of ADAs on clinical
outcomes in patients with CD who received infliximab SC maintenance
treatment. The analysis comprised 231 patients (ADA-positive:
n=150; ADA-negative: n=81) who received infliximab SC as
maintenance treatment. Notably, there were no statistically
significant differences in clinical outcomes at Week 54 between
ADA-positive and ADA-negative patients. Although mean trough serum
infliximab concentrations at Week 54 were notably lower in the
ADA-positive group than in the ADA-negative group (11.7 vs. 19.3
μg/mL; p<0.00001), both groups exceeded the historical
therapeutic target concentration of 5 μg/mL, with comparable
discontinuation rates observed between the groups.
"Results from the two-year extension phase LIBERTY studies,
alongside post-hoc analysis, highlight important data supporting
the efficacy and safety of ZYMFENTRA as a subcutaneous maintenance
treatment option for people living with CD and UC," said
Hetal Patel, Senior Director,
Medical Affairs at Celltrion USA.
"The post-hoc analysis reveals that ADAs showed no significant
impact on clinical outcomes or discontinuation rates. These
findings could be explained by the relatively high trough serum
infliximab concentrations achieved by ADA-positive
patients."[1],[2],[3]
PEREM long term study
In a large multi-center prospective cohort of inflammatory bowel
diseases, the study assessed SC infliximab persistence, efficacy
and tolerance after the switch from intravenous infliximab. The
study enrolled 426 patients, with 72.4% diagnosed with Crohn's
disease (CD). At baseline, 74% of participants were receiving the
standard IV infliximab dose (5 mg/kg every 8 weeks), with 16%
receiving combination therapy with an immunosuppressant. Drug
persistence with SC infliximab was notably high at 95.3% among
patients with complete data up to Week 48 (95% confidence interval:
93.2-97.5)[4]
About Celltrion USA
Celltrion USA is Celltrion's
U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to
innovative biologics to improve care for U.S. patients. Celltrion
currently has five biosimilars approved by the U.S. FDA:
INFLECTRA® (infliximab-dyyb),
TRUXIMA® (rituximab-abbs),
HERZUMA® (trastuzumab-pkrb),
VEGZELMA® (bevacizumab-adcd) and
YUFLYMA®(adalimumab-aaty) as well as a new biologic
ZYMFENTRA™. Celltrion USA will
continue to leverage Celltrion's unique heritage in biotechnology,
supply chain excellence and best-in-class sales capabilities to
improve access to high-quality biopharmaceuticals for U.S.
patients. For more information, please visit:
www.celltrionusa.com.
About Digestive Disease Week®
Digestive Disease Week® (DDW) is the largest
international gathering of physicians, researchers and academics in
the fields of gastroenterology, hepatology, endoscopy and
gastrointestinal surgery. Jointly sponsored by the American
Association for the Study of Liver Diseases (AASLD), the American
Gastroenterological Association (AGA), the American Society for
Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of
the Alimentary Tract (SSAT), DDW is an in-person and online meeting
from May 18-21, 2024. The meeting
showcases more than 4,400 abstracts and hundreds of lectures on the
latest advances in GI research, medicine and technology. More
information can be found at www.ddw.org
About ZYMFENTRA™ (infliximab-dyyb)
ZYMFENTRA is a prescription medicine used as an injection under
the skin (subcutaneous injection) by adults for the maintenance
treatment of: Moderately to severely active ulcerative colitis
following treatment with an infliximab product given by intravenous
infusion (IV) and moderately to severely active Crohn's
disease following treatment with an infliximab product given by
intravenous infusion (IV). ZYMFENTRA blocks the action of tumor
necrosis factor-alpha (TNF-alpha), a protein that can be
overproduced in response to certain diseases and cause the immune
system to attack normal, healthy parts of the body.
ZYMFENTRA (infliximab-dyyb) was approved by the FDA through the
Biologics License Application (BLA) under the 351 (a) pathway of
the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is a
self-injected form of infliximab and thus will be under patent
protection for its dosage form by 2037 and for its route of
administration by 2040.
ZYMFENTRA™ (infliximab-dyyb) U.S. Use and
Important Safety Information
ZYMFENTRA is a prescription medicine indicated in adults for
maintenance treatment of:
- Moderately to severely active Crohn's disease following
treatment with an infliximab product administered
intravenously.
- Moderately to severely active ulcerative colitis
following treatment with an infliximab product administered
intravenously.
It is not known if ZYMFENTRA is safe and effective in
children under 18 years of age.
What is the most important information I should know about
ZYMFENTRA?
SERIOUS INFECTIONS
Patients treated with ZYMFENTRA are at increased risk for
developing serious infections involving various organ systems and
sites that may lead to hospitalization or death. Discontinue
ZYMFENTRA if a patient develops a serious infection or
sepsis.
Reported infections include:
- Active tuberculosis (TB), including reactivation of latent
TB. Patients frequently presented with disseminated or
extrapulmonary disease. Patients should be tested for latent TB
before and during treatment with ZYMFENTRA. Treatment for latent
infection should be initiated prior to treatment with
ZYMFENTRA.
- Invasive fungal infections, including histoplasmosis,
coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and
pneumocystosis. Patients may present with disseminated, rather than
localized, disease. Empiric anti-fungal therapy should be
considered in patients at risk for invasive fungal infections who
develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic
pathogens, including Legionella and Listeria.
The risks and benefits of treatment with ZYMFENTRA should be
carefully considered prior to initiating therapy in patients with
chronic or recurrent infection. Closely monitor patients for the
development of signs and symptoms of infection during and after
treatment with ZYMFENTRA, including the possible development of TB
in patients who tested negative for latent TB infection prior to
initiating therapy.
Risk of infection may be higher in patients greater than 65
years of age, patients with comorbid conditions and/or patients
taking concomitant immunosuppressant therapy. In clinical trials,
other serious infections observed in patients treated with
infliximab included arthritis bacterial, pneumonia, and urinary
tract infection.
MALIGNANCIES
Malignancies, some fatal, have been reported in children,
adolescents, and young adults treated with TNF blockers, including
infliximab products.
Approximately half of these cases were lymphomas, including
Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a
variety of malignancies, including rare malignancies that are
usually associated with immunosuppression and malignancies that are
not usually observed in children and adolescents. The malignancies
occurred after a median of 30 months after the first dose of
therapy. Most of the patients were receiving concomitant
immunosuppressants.
Post-marketing cases of hepatosplenic T-cell lymphoma, a rare
type of T-cell lymphoma, have been reported in patients treated
with TNF blockers, including infliximab products. These cases have
had a very aggressive disease course and have been fatal. The
majority of reported cases have occurred in patients with Crohn's
disease or ulcerative colitis, and most were in adolescent and
young adult males. Almost all of these patients had received
treatment with azathioprine or 6-mercaptopurine concomitantly with
a TNF blocker at or prior to diagnosis. Carefully assess the risks
and benefits of treatment with ZYMFENTRA, especially in these
patient types.
In clinical trials of all TNF blockers, more cases of
malignancies were observed compared with controls and the expected
rate in the general population. In clinical trials of some TNF
blockers, including infliximab products, more cases of other
malignancies were observed compared with controls. As the potential
role of TNF blocker therapy in the development of malignancies is
not known, caution should be exercised when considering treatment
of patients with a current or a past history of malignancy.
Melanoma and Merkel cell carcinoma have been reported in
patients treated with TNF blocker therapy, including infliximab
products. Periodic skin examination is recommended for all
patients, particularly those with risk factors for skin cancer.
CONTRAINDICATIONS
ZYMFENTRA is contraindicated in patients with a previous severe
hypersensitivity reaction to infliximab-dyyb, other infliximab
products, any of the inactive ingredients of ZYMFENTRA or any
murine proteins (severe hypersensitivity reactions have included
anaphylaxis, hypotension, and serum sickness).
HEPATITIS B VIRUS REACTIVATION
TNF blockers, including infliximab products, have been
associated with reactivation of hepatitis B virus (HBV) in patients
who are chronic carriers. Some cases were fatal. Patients should be
tested for HBV infection before initiating ZYMFENTRA. For patients
who test positive, consult a physician with expertise in the
treatment of hepatitis B. Exercise caution when prescribing
ZYMFENTRA for patients identified as carriers of HBV, and monitor
closely for active HBV infection during and following termination
of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who
develop HBV reactivation and initiate antiviral therapy with
appropriate supportive treatment. Exercise caution when considering
resumption of ZYMFENTRA, and monitor patients closely.
HEPATOTOXICITY
Hepatobiliary disorders, including acute liver failure, jaundice
abnormal hepatic function, hepatic steatosis, hepatitis,
hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver,
have been reported in patients receiving infliximab products
post-marketing. Some cases were fatal or required liver transplant.
Aminotransferase elevations were not noted prior to discovery of
liver injury in many cases. Patients with symptoms or signs of
liver dysfunction should be evaluated for evidence of liver injury.
If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the
upper limit of normal) develop, ZYMFENTRA should be discontinued,
and a thorough investigation of the abnormality should be
undertaken.
CONGESTIVE HEART FAILURE
Cases of worsening congestive heart failure (CHF) and new onset
CHF have been reported with TNF blockers. Some cases had a fatal
outcome. In several exploratory trials of other TNF blockers in the
treatment of CHF, there were greater proportions of
TNF-blocker-treated patients who had CHF exacerbations requiring
hospitalization or increased mortality. ZYMFENTRA has not been
studied in patients with a history of CHF and ZYMFENTRA should be
used with caution in patients with CHF.
HEMATOLOGIC REACTION
Cases of leukopenia, neutropenia, thrombocytopenia, and
pancytopenia (some fatal) have been reported. The causal
relationship to infliximab-product therapy remains unclear.
Exercise caution in patients who have ongoing or a history of
significant hematologic abnormalities. Advise patients to seek
immediate medical attention if they develop signs and symptoms of
blood dyscrasias or infection. Consider discontinuation of
ZYMFENTRA in patients who develop significant hematologic
abnormalities.
HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONS
In post-marketing experience, serious systemic hypersensitivity
reactions (including anaphylaxis, hypotension, and serum sickness)
have been reported following administration of infliximab products.
If an anaphylactic or other clinically significant hypersensitivity
reaction occurs, institute appropriate therapy and discontinue
ZYMFENTRA.
INJECTION SITE REACTIONS
In clinical studies, localized injection-site reactions were
reported following administration of ZYMFENTRA. If a clinically
significant injection-site reaction occurs, institute appropriate
therapy and discontinue ZYMFENTRA.
NEUROLOGIC REACTIONS
Agents that inhibit TNF have been associated with central
nervous system (CNS) manifestation of systemic vasculitis, seizure,
and new onset or exacerbation of CNS demyelinating disorders,
including multiple sclerosis and optic neuritis, and peripheral
demyelinating disorders, including Guillain-Barré syndrome.
Exercise caution when considering ZYMFENTRA in patients with these
disorders and consider discontinuation if these disorders
develop.
RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER
BIOLOGICS PRODUCTS
Serious infections and neutropenia have been reported with
concurrent use of ZYMFENTRA with other immunosuppressive biological
products. The concurrent use of ZYMFENTRA with other
immunosuppressive biological products used to treat UC and CD may
increase the risk of infection and is not recommended.
RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR
BIOLOGICAL PRODUCTS
Consider the half-life and mode of action of prior biological
products to avoid unintended additive immunosuppressive effects
when initiating ZYMFENTRA.
AUTOIMMUNITY
Treatment with TNF blockers may result in the formation of
autoantibodies and in the development of a lupus-like syndrome.
Discontinue ZYMFENTRA treatment if symptoms of a lupus-like
syndrome develop.
VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS
AGENTS
Prior to initiating ZYMFENTRA, update vaccinations in accordance
with current vaccination guidelines. Live vaccines or therapeutic
infectious agents should not be given with ZYMFENTRA due to the
possibility of clinical infections, including disseminated
infections. At least a 6-month waiting period following birth is
recommended before the administration of any live vaccine to
infants exposed in utero to ZYMFENTRA.
ADVERSE REACTIONS
In clinical trials with ZYMFENTRA, the most common adverse
reactions occurring in ≥3% of ZYMFENTRA -treated patients included
site reactions, COVID-19, anemia, arthralgia, infection site
reaction, increased alanine aminotransferase and abdominal pain for
UC, and COVID-19, headache, upper respiratory tract infection,
injection site reaction, diarrhea, increased blood creatine
phosphokinase, arthralgia, increased alanine aminotransferase,
hypertension, urinary tract infection, neutropenia, dizziness and
leukopenia for CD.
Please click for Full U.S. Prescribing Information.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
References
[1] Jean F. Colombel et
al., Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for
Crohn's disease: 2 years results of the LIBERTY-CD study. Poster
(Su1762). Presented at DDW 2024.
|
[2] Bruce E. Sands et
al., Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis:
2-year extension results of the LIBERTY-UC study. Poster (Su1779).
Presented at DDW 2024.
|
[3] Jean F. Colombel et
al., Impact of immunogenicity on clinical outcomes in patients with
Crohn's disease receiving maintenance treatment with subcutaneous
infliximab: A post hoc analysis of the LIBERTY-CD study. Poster
(Su1765). Presented at DDW 2024.
|
[4] Nicolas Mathieu et
al., Persistence, efficacy and tolerance of subcutaneous infliximab
after switch from intravenous infliximab in IBD patients in
remission: one-year results from a multicenter prospective cohort.
Oral Presentation (1179). Presented at DDW 2024.
|
Contacts
Sarah
Amundsen
samundsen@apcoworldwide.com
+1 920-946-0918
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