– New Data Evaluating the Efficacy and
Safety Profile of Biktarvy for the Treatment of People with HIV and
Hepatitis B or Tuberculosis will be Presented –
– Retrospective Analysis Evaluating HIV
Resistance-Associated Mutations Reinforces Importance of Treatment
Selection in HIV Management –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data
from three studies evaluating the efficacy and safety profile of
Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir
alafenamide 25 mg tablets, B/F/TAF) for a broad range of people
with HIV, including those with HIV/hepatitis B (HBV) coinfection
and HIV/tuberculosis (TB) coinfection. These data and other studies
supporting the important role of Biktarvy in the HIV treatment
landscape were presented at the 31st Conference on Retroviruses and
Opportunistic Infections (CROI).
“People with HIV and comorbid conditions or pre-existing
treatment resistance can often face complex and evolving treatment
needs. These studies were conducted to help bridge the unmet HIV
treatment gap and better understand the potential of Biktarvy in a
broad range of people and communities affected by HIV and their
diverse health needs, said Jared Baeten, MD, PhD, Vice President,
HIV Clinical Development, Gilead Sciences. “The data presented at
CROI contribute to the growing body of long-term evidence for
Biktarvy and reinforce Gilead’s commitment to a person-centric
approach to HIV treatment research.”
HIV/HBV Coinfection
ALLIANCE (NCT03547908) is an ongoing Phase 3 study evaluating
the efficacy and safety of Biktarvy compared to dolutegravir 50 mg
(DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg,
F/TDF, DTG+F/TDF, in adults with HIV/HBV coinfection initiating
treatment. The ALLIANCE trial is the first randomized clinical
trial of TAF- vs TDF-based regimens in treatment naïve adults with
HIV /HBV coinfection. Its goal is to evaluate treatment regimens
that may effectively suppress both HIV and HBV. Previously reported
Week 96 results demonstrated the efficacy of both antiretroviral
regimens. Additionally, ALLIANCE participants treated with Biktarvy
exhibited numerically higher levels of HBV viral suppression and
seroconversion. Further results from the trial showed that safety
findings were similar between the Biktarvy and DTG+F/TDF groups.
Adverse events (AEs) included upper respiratory tract infection
(19.8% vs. 14.8%), COVID-19 (38% vs. 36.1%), pyrexia (12.4% vs.
13.1%), ALT increase (8.3% vs. 12.3%), and nasopharyngitis (12.4%
vs. 6.6%).
A new exploratory analysis presented at CROI further
investigated the factors associated with the HBV treatment response
observed with Biktarvy compared to DTG+F/TDF. This subgroup
analysis compared the HBV treatment responses according to baseline
demographics, HBV genotype, and markers of HIV-1/HBV disease
severity for all participants (n=243) at two years.
Consistent with the overall population, the present analysis
suggests that in people with HIV/HBV coinfection, the treatment
response of TAF- versus TDF-based therapy for many HBV treatment
outcomes may be greater for certain subgroups, supporting the
continued evaluation of Biktarvy in this population. Some of the
subgroups that showed treatment differences favoring Biktarvy
included younger age, those with certain levels or types of HBV
DNA/genotypes and those with higher-than-normal liver enzymes,
among others. The use of Biktarvy in individuals with HIV/HBV is
investigational, and the safety and efficacy of this use have not
been established.
HIV/TB Coinfection
TB is the leading cause of death among people with HIV. In 2022,
approximately 167,000 people died from HIV-associated TB, with the
WHO African Region having the highest prevalence. While significant
progress has been made in early detection and treatment of
HIV-associated TB, there are still significant therapeutic
challenges. The interactions between antiretrovirals and TB
medications complicate the management of individuals with dual
infections. These interactions primarily occur during the
metabolism of the drugs. The drug-drug interactions involving the
first-line TB drug, rifampicin, are particularly clinically
relevant for a number of antiretroviral agents.
Integrase strand transfer inhibitors (INSTIs) are recommended by
major standard guidelines for HIV treatment. Several clinical
research gaps exist when combining the INSTIs and drugs used for
the treatment of tuberculosis, which need to be addressed to inform
HIV and tuberculosis co-treatment. INSIGHT (NCT04734652) is an
ongoing Phase 2b open-label study conducted in collaboration with a
range of organizations, including the Centre for the AIDS Programme
of Research in South Africa (CAPRISA), investigating the efficacy,
safety, and pharmacokinetics of Biktarvy and dolutegravir 50 mg
(DTG) + lamivudine 300mg/ tenofovir disoproxil fumarate 300mg, TLD,
in adults initiating treatment for HIV/TB coinfection who have been
receiving a rifampicin-based treatment regimen for at least eight
weeks.
Participants were randomly allocated to receive Biktarvy or TLD
in a 2:1 ratio. Biktarvy was taken twice a day during
rifampicin-containing TB treatment and 2 weeks after stopping TB
treatment. Thereafter, Biktarvy was taken once daily. Once-daily
TLD plus dolutegravir 50mg evening dose was taken during TB
treatment and for two weeks after completion of TB treatment.
Thereafter, TLD was taken once daily – as per standard of care,
until 48 weeks. The primary outcome measure is viral suppression
rates at Week 24, defined as HIV-1 RNA ˂50 copies/mL.
Preliminary week 24 results presented at CROI showed that 97%
percent (71/73) of participants treated with Biktarvy achieved
viral suppression (HIV-1 RNA < 50 copies /ml) as did 97% (36/37)
of participants treated with the DTG-based regimen. Serious adverse
events (AEs) were common in this population with advanced HIV
disease and TB. However, none of the reported AEs were deemed
related to the study drug. A similar number of Grade 3 and Grade 4
AEs were reported in both arms.
“South Africa has the largest HIV epidemic in the world, with
more than 7 million people with HIV, over half of whom have latent
TB co-infection,” said Anushka Naidoo, BPharm, MMedSc, PhD,
Research Scientist, Centre for AIDS Programme of Research in South
Africa (CAPRISA), and Principal Investigator of the INSIGHT study.
“The availability of antiretroviral therapy options, including
within drug classes, is important, particularly in high HIV/TB
burden settings. The key findings from this landmark study
presented at CROI support the continued evaluation of Biktarvy in
people with HIV and TB as a potential treatment to bridge a
critical gap for the individuals and communities who bear the
disproportionate burden of co-infection."
The INSIGHT trial will continue through Week 48 to determine
longer-term safety and efficacy. Biktarvy is contraindicated for
coadministration with rifampin, also known as rifampicin, by the
U.S. FDA. The use of Biktarvy in individuals with HIV/TB
coinfection is investigational, and the safety and efficacy of this
use have not been established.
Resistance-Associated Mutations in
Switch Trials
Genetic changes occur in HIV by chance. Some of these changes
stop HIV medicines from working; these changes are called
resistance mutations. To understand the length of time that
resistance mutations stay in the body, researchers looked at the
genetic patterns of HIV (called HIV genotype) over time in people
who took part in three clinical studies.
Genotype data were collected at the beginning of the clinical
trials, and for some participants, earlier genotyping reports were
also available. Researchers looked at these reports to find out
whether resistance mutations persisted, newly appeared, or
disappeared in a cohort of participants (n=242) from three trials
who switched to Biktarvy treatment after achieving viral
suppression for at least three months on their previous
antiretroviral regimen.
The majority of resistance-associated mutations in the analysis
were detected 100% of the time or were newly detected and did not
disappear over time. Drug resistance mutations archived in cells
may persist despite viral suppression, posing a risk for
transmission of drug-resistant virus in cases of virological
failure, treatment interruption or non-adherence. Healthcare
providers must consider all previous drug treatments and genotype
reports and should not assume that resistance mutations are no
longer present simply because they are not reported in the most
recent genotype report, as they may reemerge at a later time. These
findings highlight the importance of understanding an individual's
treatment history and prior resistance mutation status for
treatment management.
In February 2024, the U.S. FDA approved a new, expanded
indication for Biktarvy to treat virologically suppressed people
with HIV with M184V/I resistance, a common form of treatment
resistance.
Additional research studies evaluating Biktarvy presented at
CROI 2024 explore safety and efficacy data in older populations, as
well as treatment effects on immune activation biomarkers and
weight change in people with HIV who are virologically
suppressed.
Please see below for U.S. Indications and Important Safety
Information for Biktarvy, including BOXED WARNING.
There is currently no cure for HIV or AIDS.
About
Biktarvy
Biktarvy is a complete HIV treatment that combines three
powerful medicines to form the smallest 3-drug, integrase strand
transfer inhibitor (INSTI)-based single-tablet regimen (STR)
available, offering simple once-daily dosing with or without food,
with a limited drug interaction potential and a high barrier to
resistance. Biktarvy combines the novel, unboosted INSTI
bictegravir, with the Descovy® (emtricitabine 200 mg/tenofovir
alafenamide 25 mg tablets, F/TAF) backbone. Biktarvy is a complete
STR and should not be taken with other HIV medicines.
U.S. Indication for
Biktarvy
Biktarvy is indicated as a complete regimen for the treatment of
human immunodeficiency virus type 1 (HIV-1) infection in adults and
pediatric patients weighing at least 14 kg who have no
antiretroviral (ARV) treatment history or to replace the current
ARV regimen in those who are virologically-suppressed (HIV-1 RNA
<50 copies per mL) on a stable ARV regimen with no known or
suspected substitutions associated with resistance to bictegravir
or tenofovir.
U.S. Important Safety Information for
Biktarvy
BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS
B
- Severe acute exacerbations of hepatitis B have been reported
in patients who are coinfected with HIV-1 and HBV and have
discontinued products containing emtricitabine (FTC) and/or
tenofovir disoproxil fumarate (TDF), and may occur with
discontinuation of BIKTARVY. Closely monitor hepatic function with
both clinical and laboratory follow-up for at least several months
in patients who are coinfected with HIV-1 and HBV and discontinue
BIKTARVY. If appropriate, anti-hepatitis B therapy may be
warranted.
Contraindications
- Coadministration: Do not use BIKTARVY with dofetilide or
rifampin.
Warnings and precautions
- Drug interactions: See Contraindications and Drug
Interactions sections. Consider the potential for drug interactions
prior to and during BIKTARVY therapy and monitor for adverse
reactions.
- Immune reconstitution syndrome, including the occurrence
of autoimmune disorders with variable time to onset, has been
reported.
- New onset or worsening renal impairment: Postmarketing
cases of renal impairment, including acute renal failure, proximal
renal tubulopathy (PRT), and Fanconi syndrome have been reported
with tenofovir alafenamide (TAF)–containing products. Do not
initiate BIKTARVY in patients with estimated creatinine clearance
(CrCl) <30 mL/min except in virologically suppressed adults
<15 mL/min who are receiving chronic hemodialysis. Patients with
impaired renal function and/or taking nephrotoxic agents (including
NSAIDs) are at increased risk of renal-related adverse reactions.
Discontinue BIKTARVY in patients who develop clinically significant
decreases in renal function or evidence of Fanconi syndrome. Renal
monitoring: Prior to or when initiating BIKTARVY and during
therapy, assess serum creatinine, CrCl, urine glucose, and urine
protein in all patients as clinically appropriate. In patients with
chronic kidney disease, assess serum phosphorus.
- Lactic acidosis and severe hepatomegaly with steatosis:
Fatal cases have been reported with the use of nucleoside analogs,
including FTC and TDF. Discontinue BIKTARVY if clinical or
laboratory findings suggestive of lactic acidosis or pronounced
hepatotoxicity develop, including hepatomegaly and steatosis in the
absence of marked transaminase elevations.
Adverse reactions
- Most common adverse reactions (incidence ≥5%; all
grades) in clinical studies through week 144 were diarrhea (6%),
nausea (6%), and headache (5%).
Drug interactions
- Prescribing information: Consult the full prescribing
information for BIKTARVY for more information on Contraindications,
Warnings, and potentially significant drug interactions, including
clinical comments.
- Enzymes/transporters: Drugs that induce P-gp or induce
both CYP3A and UGT1A1 can substantially decrease the concentration
of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or
inhibit both CYP3A and UGT1A1 may significantly increase the
concentrations of components of BIKTARVY. BIKTARVY can increase the
concentration of drugs that are substrates of OCT2 or MATE1.
- Drugs affecting renal function: Coadministration of
BIKTARVY with drugs that reduce renal function or compete for
active tubular secretion may increase concentrations of FTC and
tenofovir and the risk of adverse reactions.
Dosage and administration
- Dosage: Adult and pediatric patients weighing ≥25 kg: 1
tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine
(FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with
or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1
tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once
daily with or without food. For children unable to swallow a whole
tablet, the tablet can be split and each part taken separately as
long as all parts are ingested within approximately 10
minutes.
- Renal impairment: For patients weighing ≥25 kg, not
recommended in patients with CrCl 15 to <30 mL/min, or <15
mL/min who are not receiving chronic hemodialysis, or <15 mL/min
who are receiving chronic hemodialysis and have no antiretroviral
treatment history. For patients weighing ≥14 kg to <25 kg, not
recommended in patients with CrCl <30 mL/min.
- Hepatic impairment: Not recommended in patients with
severe hepatic impairment.
- Prior to or when initiating: Test patients for HBV
infection.
- Prior to or when initiating, and during treatment: As
clinically appropriate, assess serum creatinine, CrCl, urine
glucose, and urine protein in all patients. In patients with
chronic kidney disease, assess serum phosphorus.
Pregnancy and lactation
- Pregnancy: There is insufficient human data on the use
of BIKTARVY during pregnancy. Dolutegravir, another integrase
inhibitor, has been associated with neural tube defects. Discuss
the benefit-risk of using BIKTARVY during pregnancy and conception.
An Antiretroviral Pregnancy Registry (APR) has been established.
Available data from the APR for FTC shows no difference in the
rates of birth defects compared with a US reference
population.
- Lactation: Women infected with HIV-1 should be
instructed not to breastfeed, due to the potential for HIV-1
transmission.
About Gilead Sciences in
HIV
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis, COVID-19, and cancer. Gilead operates in more than
35 countries worldwide, with headquarters in Foster City,
California.
For more than 35 years, Gilead has been a leading innovator in
the field of HIV, driving advances in treatment, prevention and
cure research. Gilead researchers have developed 12 HIV
medications, including the first single-tablet regimen to treat
HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP)
to help reduce new HIV infections, and the first long-acting
injectable HIV treatment medication administered twice-yearly. Our
advances in medical research have helped to transform HIV into a
treatable, preventable, chronic condition for millions of
people.
Gilead is committed to continued scientific innovation to
provide solutions for the evolving needs of people affected by HIV
around the world. Through partnerships, collaborations and
charitable giving, the company also aims to improve education,
expand access and address barriers to care, with the goal of ending
the HIV epidemic for everyone, everywhere. Gilead was recognized as
the number one philanthropic funder of HIV-related programs in a
report released by Funders Concerned About AIDS.
Learn more about Gilead’s unique collaborations worldwide and
the work to help end the global HIV epidemic.
Forward-Looking
Statements
This press release includes forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including Gilead’s ability to initiate, progress or complete
clinical trials or studies within currently anticipated timelines
or at all, and the possibility of unfavorable results from ongoing
and additional clinical trials or studies, including those
involving Biktarvy; uncertainties relating to regulatory
applications and related filing and approval timelines, including
potential applications for indications currently under evaluation;
the possibility that Gilead may make a strategic decision to
discontinue development of these programs and, as a result, these
programs may never be successfully commercialized for the
indications currently under evaluation; and any assumptions
underlying any of the foregoing. These and other risks,
uncertainties and factors are described in detail in Gilead’s
Annual Report on Form 10-K for the year ended December 31, 2023, as
filed with the U.S. Securities and Exchange Commission. These
risks, uncertainties and other factors could cause actual results
to differ materially from those referred to in the forward-looking
statements. All statements other than statements of historical fact
are statements that could be deemed forward-looking statements. The
reader is cautioned that any such forward-looking statements are
not guarantees of future performance and involve risks and
uncertainties and is cautioned not to place undue reliance on these
forward-looking statements. All forward-looking statements are
based on information currently available to Gilead, and Gilead
assumes no obligation and disclaims any intent to update any such
forward-looking statements.
U.S. Prescribing
Information for Biktarvy, including BOXED WARNING, is
available at www.gilead.com.
Biktarvy, Gilead and the Gilead logo are
registered trademarks of Gilead Sciences, Inc., or its related
companies.
For more information about Gilead, please visit
the company’s website at www.gilead.com,
follow Gilead on Twitter (@Gilead Sciences) and LinkedIn, or call
Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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version on businesswire.com: https://www.businesswire.com/news/home/20240306036015/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Media public_affairs@gilead.com
Gilead Sciences (NASDAQ:GILD)
過去 株価チャート
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Gilead Sciences (NASDAQ:GILD)
過去 株価チャート
から 5 2023 まで 5 2024