– New Positive Clinical Data Demonstrate
Momentum on Investigational Once-Daily, Once-Weekly and
Twice-Yearly Dosing Strategies –
– Key Findings from Studies Evaluating
Potential Future Long-Acting Combination Regimens Affirm Commitment
to Continuous Biomedical Innovation –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced the
presentation of key data highlighting the breadth of its innovative
HIV treatment research pipeline. The latest results explore
clinical outcomes from a study evaluating an investigational
combination regimen of bictegravir and lenacapavir, new findings
from a study evaluating the investigational combination of
lenacapavir with broadly neutralizing antibodies (bNAbs), and new
proof-of-concept data on GS-1720, a novel once-weekly integrase
strand transfer inhibitor (INSTI). The data presented at the 31st
Conference on Retroviruses and Opportunistic Infections (CROI)
demonstrate Gilead’s commitment to advancing the next wave of
biomedical innovations in HIV to address the unmet needs of people
with the virus and help end the epidemic worldwide.
“The latest findings across our HIV pipeline showcase the
potential of multiple candidates to help transform HIV management,”
said Jared Baeten, MD, PhD, Vice President, HIV Clinical
Development, Gilead Sciences. “Exploring a broad range of agents
with different dosing frequencies and administration methods is a
fundamental aspect of Gilead’s research and development program. By
working to provide more options that aim to enhance adherence, we
can help more individuals achieve sustained viral suppression, and
further help reduce the transmissible virus pool at the population
level.”
Oral, Once-Daily Combination of Bictegravir and
Lenacapavir
ARTISTRY-1 (NCT05502341) is an ongoing, open-label, multicenter
Phase 2/3 study being conducted to compare the investigational
once-daily combination of bictegravir, an integrase strand transfer
inhibitor, and lenacapavir, a first-in-class capsid inhibitor,
versus current therapy in people with HIV who are virologically
suppressed on complex regimens. It is estimated that up to 10% of
people with HIV take a complex treatment regimen, defined as 2 or
more pills each day. While single-tablet regimens for HIV have been
available for well over a decade, some individuals cannot take a
single-tablet option, although studies have found greater adherence
for one pill, once daily options.
In new Phase 2 data, 128 participants on a stable baseline
regimen for six or more months prior to screening were randomly
allocated in a 2:2:1 ratio to receive once-daily oral bictegravir
75 mg + lenacapavir 25 mg (n=51), bictegravir 75 mg + lenacapavir
50 mg (n=52) or continue their current stable baseline regimen
(n=25). The primary endpoint was the proportion of patients without
virologic suppression (HIV viral load ≥50 copies/mL per FDA
Snapshot) at Week 24. Key secondary endpoints included the
proportion of participants with virologic suppression (HIV viral
load ≤50 copies/mL per FDA Snapshot) and the proportion of
participants with treatment-emergent adverse events (TEAEs).
Results showed that all three treatment groups had robust
virologic suppression at six months, with consistently low viral
loads throughout the study. None of the participants in the
lower-dose lenacapavir group or the stable baseline regimen group
experienced viral load rebound (≥50 copies/mL) through Week 24. In
the higher dose lenacapavir group, only one participant had a viral
load increase above the threshold, which was later suppressed
without changing the regimen.
Additionally, both bictegravir + lenacapavir regimens exhibited
favorable safety profiles with similar rates of TEAEs. Up to Week
24, the most common TEAEs in these groups were diarrhea (7%),
COVID-19 (6%), and constipation (5%). Drug-related TEAEs leading to
discontinuation were reported in 2% of participants receiving
bictegravir 75 mg + lenacapavir 50 mg, 2% receiving bictegravir 75
mg + lenacapavir 25 mg, and none in the stable baseline regimen
group.
The findings help support the efficacy and safety profile of
switching individuals with HIV on complex regimens to a potentially
less complex combination of bictegravir and lenacapavir. This
investigational combination is being further evaluated as a
single-tablet regimen in the Phase 3 portion of the ARTISTRY-1
study.
Twice-Yearly Dosing with Lenacapavir and bNAbs
In a recent Phase 1b study published in The Lancet HIV, the
investigational combination of lenacapavir + teropavimab (GS-5423,
TAB) + zinlirvimab (GS-2872, ZAB) demonstrated high efficacy and
maintained virologic suppression for six months with twice-yearly
dosing. To follow up on the potential of this long-acting
combination, an additional cohort to the Phase 1B study was added
to evaluate the regimen in an expanded population of virologically
suppressed adults with HIV on ARV for 18 months or longer with
high-level sensitivity to either bNAb, but not both, to determine
whether sensitivity to either bNAb impacts the safety profile or
efficacy of this investigational combination approach.
Doses of TAB and ZAB were weight-based. All participants
received lenacapavir (927 mg subcutaneously after oral loading) +
TAB (30 mg/kg intravenously [IV]) and were randomly allocated in a
1:1 ratio to receive two different ZAB doses (Group 1, 10 mg/kg IV;
Group 2, 30 mg/kg IV). Eleven participants were randomized and
treated (Group 1, n=5; Group 2, n=6). Age range was 28–63 years;
3/11 were female; 4/11 were Black; & median CD4 count was 916
cells/µL.
At six months, the investigational long-acting combination of
lenacapavir + TAB + ZAB was well tolerated, had a favorable safety
profile, and maintained virologic suppression (HIV viral load ≤50
copies/mL) in 8/10 of participants. In addition, each of the six
participants in the higher-dose ZAB group maintained virologic
suppression at six months, showing the potential of this
investigational long-acting treatment regimen with twice-yearly
dosing.
Of the two participants who experienced virologic rebound, one
was diagnosed with acute COVID-19 at the time of rebound, and one
rebounded at Week 26. Both had HIV RNA below 100 copies at Week 26.
Additionally, one participant restarted baseline antiretroviral
therapy due to a protocol violation and was excluded from the
efficacy analysis. Safety outcomes were similar between the two
groups, and no AEs led to discontinuation of the study drug. There
was one instance of a serious adverse event, which involved a soft
tissue infection unrelated to study treatment.
The investigational combination of lenacapavir + TAB + ZAB has
advanced to a Phase 2 study (NCT05729568). Evaluating the
combination in virologically suppressed people with HIV, the study
will assess safety and efficacy of the regimen in virologically
suppressed participants followed longitudinally for multiple doses
of the study regimen.
An additional observational study from the PRESTIGIO registry
investigated susceptibility to the bNAbs TAB and ZAB in individuals
with multidrug-resistant (MDR) HIV, who were resistant to four drug
classes and may have limited options. In approximately 40% of
participants, the virus was susceptible to TAB and ZAB, indicating
that certain individuals living with multi-drug resistant HIV may
be suitable candidates for future trials investigating long-acting
regimens containing TAB and ZAB.
Long-Acting, Once-Weekly Dosing
New clinical data featured in a late-breaker oral presentation
at CROI demonstrate the first proof of concept that an integrase
strand transfer inhibitor (INSTI) has a pharmacokinetic profile
suitable for a weekly dosing interval. GS-1720 is a selective INSTI
being evaluated as a novel, investigational once-weekly
antiretroviral agent in combination with long-acting agents with a
goal to provide people with HIV with new long-acting options.
The ongoing Phase 1b open-label trial is being conducted in
participants with HIV who are treatment-naïve or viremic and off
antiretroviral therapy for at least 12 weeks. Twenty-eight people
with HIV were randomly allocated to receive doses of GS-1720 (30,
150, 450, or 900 mg) on Day 1 and Day 2 and followed for 10 days.
The primary endpoint was the maximum reduction of plasma HIV-1 RNA
through post-dose Day 11. Results were presented for each of the
four treatment cohorts.
GS-1720 demonstrated potential antiviral activity in those
participants dosed above 150mg compared to baseline. GS-1720 was
generally well tolerated. No participants experienced any serious
AEs, Grade 3 or higher TEAEs, or AEs related to study drug. No
treatment emergent INSTI resistance was observed at Day 11 for the
450mg and 150mg cohorts; resistance testing is ongoing for the
other dose cohorts. These findings support the continued clinical
evaluation of GS-1720 as part of a potential novel once-weekly oral
HIV treatment option.
Gilead’s goal is to discover and develop innovative HIV
medicines. We believe the next wave of innovation in HIV includes
long-acting options that are aiming to help address the
differentiated needs and preferences of the diverse range of
individuals and communities affected by the epidemic. Optionality
is critical for those who are not able to adhere to current
regimens and for helping people with HIV, regardless of where they
find themselves on the continuum of care, to improve their
individual outcomes and advance public health.
Teropavimab (GS-5423, TAB), zinlirvimab (GS-2872, ZAB), and
GS-1720 are investigational compounds and are not approved by the
U.S. Food and Drug Administration or any other regulatory authority
for any use. The use of these compounds alone or in combination
with lenacapavir are investigational. Their safety and efficacy are
unknown.
Bictegravir and lenacapavir in combination are investigational
and not approved anywhere globally. Their safety and efficacy have
not yet been established.
Lenacapavir, marketed as Sunlenca®, is approved in 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.
There is currently no cure for HIV or AIDS.
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. 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 would
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 have not been established.
Lenacapavir is being evaluated as a long-acting option in multiple
ongoing and planned early and late-stage clinical studies in
Gilead’s HIV prevention and treatment research program.
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.
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 bictegravir, lenacapavir, teropavimab, zinlirvimab, and
GS-1720; 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. full Prescribing Information for Sunlenca
is available at www.gilead.com
Sunlenca, 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/20240304716860/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Media public_affairs@gilead.com
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