– Week 24 Results Support Continued
Development as a Potential Long-Acting Oral Combination Treatment
Option in Virologically Suppressed People with HIV –
– Novel Investigational Combination Regimen
has the Potential to be the First Oral Weekly HIV Treatment,
Helping to Address Unmet Needs –
Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK),
known as MSD outside of the United States and Canada, today
announced results from the Phase 2 clinical study evaluating the
investigational combination of islatravir, an investigational
nucleoside reverse transcriptase translocation inhibitor, and
lenacapavir, a first-in-class capsid inhibitor. These late-breaking
data were presented during an oral session at the 31st Conference
on Retroviruses and Opportunistic Infections (CROI). Prior to the
late-breaker oral presentation, the key findings were featured in a
CROI press conference.
At 24 weeks, the novel investigational combination maintained a
high rate (94.2%) of viral suppression (HIV-1 RNA <50
copies/mL), which is a secondary endpoint of the study. Results of
the primary endpoint (HIV-1 RNA ≥50 copies/mL (c/mL) showed that
one participant (1.9%) treated with islatravir and lenacapavir had
a viral load of >50 copies/mL at Week 24; the participant later
suppressed on islatravir and lenacapavir at Week 30.
The potent antiviral activities, along with pharmacokinetic
profiles of islatravir and lenacapavir, support their development
as an investigational once-weekly oral combination regimen.
Single-tablet daily oral therapies have helped to transform HIV
care, but options that allow for less frequent dosing have the
potential to address adherence, stigma and other challenges faced
by some individuals taking daily oral antiretroviral therapy.
“HIV treatment is not one size fits all – developing once-weekly
treatment options could help meet the needs of each individual,
aiming toward maximizing long-term outcomes for people with HIV,”
said Jared Baeten, Vice President, MD, PhD, HIV Clinical
Development, Gilead Sciences. “These promising data presented at
CROI help bring us one step closer to our goal of providing a wide
range of options that may help transform the HIV treatment
landscape.”
In this open-label, active-controlled study (NCT05052996),
virologically suppressed adults (n=104) on Biktarvy® (bictegravir
50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets,
B/F/TAF) were randomly allocated in a 1:1 ratio to receive either
oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or
to continue daily oral Biktarvy (n=52). The median age of
participants was 40 years. Eighteen percent of participants were
assigned female at birth, 50% were non-white, and 29% were Hispanic
or Latinx.
Results of the primary endpoint, measured as HIV-1 RNA ≥50
copies/mL (c/mL) at Week 24 per FDA Snapshot algorithm, showed that
one participant (1.9%) treated with islatravir and lenacapavir had
a viral load of more than 50 copies/mL at Week 24; the participant
later suppressed on islatravir and lenacapavir at Week 30. No
participants in the Biktarvy group had a viral load of more than 50
copies/mL at Week 24. Results of the secondary endpoint, as
measured by the proportion of individuals with HIV-1 RNA < 50
c/mL at Week 24, showed that participants who switched to treatment
with once-weekly islatravir and lenacapavir or continued Biktarvy
both maintained comparable high rates of HIV suppression at Week 24
(94.2% v. 94.2%).
Grade 1 and 2 treatment-related-adverse events (TRAEs) reported
in the islatravir and lenacapavir group included dry mouth and
nausea (each 3.8%). No grade 1 and 2 TRAEs were reported in the
Biktarvy group. No grade 3 or 4 TRAEs related to study drug in
either treatment group were reported. Two participants discontinued
islatravir and lenacapavir due to adverse events unrelated to the
drug. In addition, no differences were seen between treatment
groups for changes in CD4+ T cell counts or absolute lymphocyte
counts.
“Our strategies for managing and treating HIV must evolve with
the needs of the HIV community and we are excited to have these
promising first data from the Phase 2 study for islatravir and
lenacapavir presented at CROI,” said Dr. Elizabeth Rhee, vice
president, global clinical development, Merck Research
Laboratories. “Gilead and Merck remain committed to this
collaboration and to the development of a potential once-weekly
oral therapy for people living with HIV who may need additional
options to help maintain viral suppression.”
The Phase 2 study will continue in an open-label fashion through
Week 48. Longer-term data will be presented at a future scientific
conference.
Islatravir, alone or in combination with lenacapavir, is
investigational and not approved anywhere globally. The safety and
efficacy of the combination of islatravir and lenacapavir have not
been established.
Lenacapavir, marketed as Sunlenca®, is approved in Australia,
Canada, the European Union, Israel, Japan, Switzerland, the United
Arab Emirates, the United Kingdom and the United States for the
treatment of people with multi-drug resistant HIV in combination
with other antiretroviral(s).
Please see below for the U.S. Indication and Important Safety
Information for Sunlenca. Please also see below for U.S. Indication
and Important Safety Information, including Boxed Warning, for
Biktarvy.
There is currently no cure for HIV or AIDS.
About islatravir
(MK-8591)
Islatravir (MK-8591) is Merck’s investigational nucleoside
reverse transcriptase translocation inhibitor under evaluation for
the treatment of HIV-1 in combination with other antiretrovirals.
For an overview of Merck’s HIV treatment and prevention clinical
development program, please click here.
About Sunlenca®
Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection)
[(lenacapavir)] is a first-in-class, long-acting HIV capsid
inhibitor indicated for the treatment of HIV infection, in
combination with other antiretroviral(s), in adults with multi-drug
resistant HIV who are heavily treatment-experienced. Sunlenca is
the only HIV treatment option administered twice-yearly. Sunlenca
tablets are approved for oral loading during initiation of Sunlenca
treatment, prior to or at the time of the first long-acting
lenacapavir injection depending on initiation option.
The multi-stage mechanism of action of Sunlenca’s active
pharmaceutical agent, lenacapavir, is distinguishable from other
currently approved classes of antiviral agents. While most
antivirals act on just one stage of viral replication, Sunlenca is
designed to inhibit HIV at multiple stages of its lifecycle and has
no known cross resistance exhibited in vitro to other existing drug
classes.
Lenacapavir is being developed as a foundation for future HIV
therapies developed by Gilead. The goal is to offer both
long-acting oral and injectable options with various dosing
frequencies in combination with other antiretroviral agents for
treatment or as a single agent for prevention. This approach aims
to help address the individual needs and preferences of people with
HIV and people who could benefit from pre-exposure prophylaxis
(PrEP). The use of lenacapavir for HIV prevention is
investigational and the safety and efficacy of lenacapavir for this
use has not been established. Lenacapavir is being evaluated as a
potential long-acting option in multiple ongoing and planned early
and late-stage clinical studies in Gilead’s HIV prevention and
treatment research program.
About Merck
At Merck, known as MSD outside of the United States and Canada,
we are unified around our purpose: We use the power of leading-edge
science to save and improve lives around the world. For more than
130 years, we have brought hope to humanity through the development
of important medicines and vaccines. We aspire to be the premier
research-intensive biopharmaceutical company in the world – and
today, we are at the forefront of research to deliver innovative
health solutions that advance the prevention and treatment of
diseases in people and animals. We foster a diverse and inclusive
global workforce and operate responsibly every day to enable a
safe, sustainable and healthy future for all people and
communities. For more information, visit www.merck.com and connect
with us on X (formerly Twitter), Facebook, Instagram, YouTube and
LinkedIn.
Merck’s Commitment to
HIV
For more than 35 years, Merck has been committed to scientific
research and discovery in HIV. Today, we are developing a series of
antiviral options designed to help people manage HIV and protect
people from HIV, with the goal of reducing the growing burden of
infection worldwide. We remain committed to collaborating with
others in the global HIV community to address the complex
challenges that impede progress toward ending the epidemic.
About Gilead Sciences in
HIV
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 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.
U.S. Indication for
Sunlenca
Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid
inhibitor, in combination with other antiretroviral(s), is
indicated for the treatment of HIV-1 infection in heavily
treatment-experienced adults with multidrug resistant HIV-1
infection failing their current antiretroviral regimen due to
resistance, intolerance, or safety considerations.
U.S. Important Safety Information for
Sunlenca
Contraindications
- Coadministration: Concomitant administration of SUNLENCA
is contraindicated with strong CYP3A inducers.
Warnings and precautions
- Immune reconstitution syndrome, including the occurrence
of autoimmune disorders with variable time to onset, has been
reported in patients treated with combination antiretroviral (ARV)
therapy.
- Long-acting properties and potential associated risks with
SUNLENCA: Residual concentrations of SUNLENCA may remain in the
systemic circulation of patients for up to 12 months or longer.
SUNLENCA may increase exposure, and potential risk of adverse
reactions, to drugs primarily metabolized by CYP3A initiated within
9 months after last injection. Counsel patients regarding the
dosing schedule because nonadherence could lead to loss of
virologic response and development of resistance. If virologic
failure occurs, switch to an alternative regimen if possible. If
discontinuing SUNLENCA, begin alternate suppressive ARV regimen
within 28 weeks from last injection.
- Injection site reactions may occur, and nodules and
indurations may be persistent.
Adverse reactions
- Most common adverse reactions (incidence ≥3%, all
grades) are injection site reactions (65%) and nausea (4%).
Drug interactions
- Prescribing information: Consult the full prescribing
information for SUNLENCA for more information on Contraindications,
Warnings, and potentially significant drug interactions, including
clinical comments.
- Enzymes/transporters: Drugs that are strong or moderate
inducers of CYP3A may significantly decrease the concentration of
SUNLENCA. Drugs that strongly inhibit CYP3A, P-gp, and UGT1A1
together may significantly increase the concentration of SUNLENCA.
SUNLENCA may increase the exposure of drugs primarily metabolized
by CYP3A, when initiated within 9 months after the last injection
of SUNLENCA, which may increase the potential risk of adverse
reactions.
Dosage and administration
- Dosage: Initiation with 1 of 2 options, followed by
maintenance dosing once every 6 months. Tablets may be taken with
or without food.
- Initiation Option 1: Day 1: 927 mg by subcutaneous
injection and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg
orally (2 x 300-mg tablets).
- Initiation Option 2: Day 1: 600 mg orally (2 x 300-mg
tablets). Day 2: 600 mg orally (2 x 300-mg tablets). Day 8: 300 mg
orally (1 x 300-mg tablet). Day 15: 927 mg by subcutaneous
injection.
- Maintenance: 927 mg by subcutaneous injection every 26
weeks +/- 2 weeks from date of last injection.
- Missed Dose: During the maintenance period, if more than
28 weeks have elapsed since the last injection and if clinically
appropriate to continue SUNLENCA treatment, restart the initiation
dosage regimen from Day 1, Option 1 or Option 2.
Pregnancy and lactation
- Pregnancy: There is insufficient human data on the use
of SUNLENCA during pregnancy. An Antiretroviral Pregnancy Registry
(APR) has been established.
- Lactation: Individuals infected with HIV-1 should be
instructed not to breastfeed, due to the potential for HIV-1
transmission.
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 treatment history or to replace the current
antiretroviral regimen in those who are virologically-suppressed
(HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral
regimen with no history of treatment failure and 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.
Gilead 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 and lenacapavir; 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.
Forward-Looking Statement of Merck
& Co., Inc., Rahway, N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA
(the “company”) includes “forward-looking statements” within the
meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline candidates that
the candidates will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s Annual
Report on Form 10-K for the year ended December 31, 2023 and the
company’s other filings with the Securities and Exchange Commission
(SEC) available at the SEC’s Internet site (www.sec.gov).
U.S. full Prescribing Information for Biktarvy,
including BOXED WARNING, and U.S. full Prescribing
Information for Sunlenca are available at www.gilead.com.
Biktarvy, Sunlenca, Gilead and the Gilead logo
are registered trademarks of Gilead Sciences, Inc., or its related
companies. All other marks are the property of their respective
owners.
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/20240305598604/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Media public_affairs@gilead.com
Peter Dannenbaum, Investors peter.dannenbaum@merck.com
Julie Cunningham, Media julie.cunningham@merck.com
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