– Newly Presented Results, to be Published
in The New England Journal of Medicine, Include Adherence and
Pharmacokinetics Data; Data Underscore High Efficacy and Safety
Profile of Lenacapavir Among Broad and Geographically Diverse Range
of Individuals –
– FDA Recently Granted Breakthrough Therapy
Designation for Lenacapavir for PrEP; Gilead to Begin Regulatory
Filings by End of 2024 –
– Gilead Spearheading Lenacapavir Access
Strategies to Ensure Scientific Innovation Translates to
Global Access and Real-World Impact –
Gilead Sciences, Inc. (Nasdaq: GILD) today presented the first
in-depth look at full results from its pivotal Phase 3 PURPOSE 2
trial (NCT04925752), which is studying twice-yearly lenacapavir,
the company’s injectable HIV-1 capsid inhibitor, for the
investigational use of HIV prevention among a broad and
geographically diverse range of cisgender men and gender-diverse
people. Newly presented results include data on adherence to and
pharmacokinetics of lenacapavir among trial participants.
The data were presented during an oral abstract session at the
International Congress on Drug Therapy in HIV Infection (HIV
Glasgow) and will be published in The New England Journal of
Medicine. The release of the full PURPOSE 2 data follows the
unblinding of the trial at interim analysis in September and a
presentation of additional efficacy and safety data last month at
the HIV Research for Prevention Conference in Lima, Peru. Those
previously reported data showed that lenacapavir reduced HIV
infections by 96% compared to background HIV incidence (bHIV), with
two incident cases among 2,179 participants, corresponding to 99.9%
of participants not acquiring HIV infection in the lenacapavir
group. Twice-yearly lenacapavir also demonstrated superiority to
once-daily Truvada® (emtricitabine 200 mg and tenofovir disoproxil
fumarate 300 mg; F/TDF) for pre-exposure prophylaxis (PrEP) and was
generally well-tolerated, with no significant or new safety
concerns identified.
“We’re at a crossroads in the HIV epidemic, and a twice-yearly
choice for HIV prevention, if approved, could be transformative as
we work toward achieving the UNAIDS 2030 targets around the world,”
said PURPOSE 2 Principal Investigator Onyema Ogbuagu, MBBCh, FACP,
FIDSA, Associate Professor of Medicine and Pharmacology at Yale
School of Medicine and Director of the Yale Antivirals and Vaccines
Research Program. “Lenacapavir for PrEP could provide an important
alternative to existing preventative medications that require more
frequent dosing, and could help transform the HIV prevention
landscape by addressing a range of unmet needs for individuals who
need or want PrEP globally.”
Participants demonstrated high adherence to lenacapavir and
injections
Adherence to lenacapavir and to the placebo injections that were
part of the oral PrEP study group was high: 91.0% of all trial
participants received on-time injections at week 26, and 92.8% of
participants received on-time injections at one year. On-time
injection rates (within 28 weeks of prior injection) were similar
across both study groups, whether receiving lenacapavir or placebo
injections.
Lenacapavir reduced HIV infections by 96% compared to
background HIV incidence (bHIV)
Lenacapavir was highly effective at reducing HIV infections
among trial participants: 99.9% of participants did not acquire HIV
in the lenacapavir group, with two incident cases among 2,179
participants (0.10/100 person-years, 95% CI, 0.01 to 0.37), despite
reported high levels of sexual behavior, chemsex and sexually
transmitted infections observed among PURPOSE 2 participants. The
results demonstrated superiority of twice-yearly lenacapavir over
bHIV (2.37/100 person-years, 95% CI, 1.65 to 3.42; primary
endpoint), with 96% relative risk reduction (IRR 0.04; 95% CI, 0.01
to 0.18; p<0.0001). Additionally, twice-yearly lenacapavir was
89% more effective at reducing HIV infections than once-daily
Truvada (IRR 0.11; 95% CI, 0.02 to 0.51; p=0.00245).
Lenacapavir plasma concentrations for the two participants who
acquired HIV in this group were within the range of the overall
lenacapavir concentrations in the pre-selected, representative
subset of participants whose blood plasma levels were tested.
Lenacapavir plasma concentrations were also similar to those in
prior studies that included lenacapavir. Trial data confirm that
both participants acquired HIV after receiving their first
injections of lenacapavir but prior to their second injections, and
both participants were diagnosed using standard HIV tests.
Importantly, based on retrospective standard HIV-1 RNA viral load
testing of prior visit samples, there was no delayed HIV diagnosis
for either person. The HIV PrEP field has paid particular attention
to the potential for delayed diagnosis for individuals who acquire
HIV when using long-acting PrEP.
Cases of HIV infection despite high adherence to other forms of
PrEP, including Truvada, have been reported, often in the context
of high exposures to HIV and repeated mucosal injury. Gilead has
offered open-label lenacapavir to all trial participants in PURPOSE
1 (evaluating lenacapavir for PrEP among cisgender women) and is
offering open-label lenacapavir to all participants in PURPOSE 2,
and will continue to follow participants and test for incident HIV
infection.
Truvada adherence was initially high but declined over
time
Adherence to Truvada, measured through detection of tenofovir
diphosphate in blood samples from a subset of random participants,
was initially high but declined over time: tenofovir diphosphate
levels consistent with high adherence (four or more tablets per
week) were seen in 82% of participants at week 8, 67% at week 26
and 62% at one year.
In the Truvada group, nine incident HIV infections occurred,
all in participants with low or no adherence
There were nine incident cases among 1,086 individuals in the
Truvada group (0.93/100 person-years; 95% CI, 0.43 to 1.77;
secondary endpoint). These nine participants had evidence of low or
no adherence to Truvada, or had discontinued taking it more than 10
days prior to diagnosis. Among the nine participants, two had low
levels of tenofovir diphosphate, six had levels below the
quantification limit, and one person who was missing a dried blood
spot sample had discontinued Truvada.
PURPOSE 2 trial background
PURPOSE 2 is a Phase 3, double-blind, multicenter, randomized
study evaluating the safety and efficacy of twice-yearly
subcutaneous lenacapavir for PrEP versus bHIV and once-daily oral
Truvada in 3,271 cisgender gay, bisexual, and other men,
transgender women, transgender men, and gender non-binary
individuals aged 16 years or older who have sex with partners
assigned male at birth. The trial spanned 88 sites in Argentina,
Brazil, Mexico, Peru, South Africa, Thailand and the United States,
and participants were randomized in a 2:1 ratio to lenacapavir and
Truvada, respectively. Because effective PrEP options already
exist, there is broad consensus in the PrEP field that a placebo
group would be unethical; thus, the trial used bHIV as the primary
comparator and Truvada as a secondary comparator.
PURPOSE 2 is the second pivotal Phase 3 trial to demonstrate
superior efficacy for twice-yearly lenacapavir for the
investigational use of HIV prevention as PrEP, and to be unblinded
early because it met its key efficacy endpoints. In June 2024, the
PURPOSE 1 trial (NCT04994509), studying lenacapavir for PrEP among
cisgender women in sub-Saharan Africa, was also unblinded early
because it met its key efficacy endpoints.
Gilead continues to focus on global access strategies,
including for low-, middle- and high-income countries
Data from both PURPOSE 1 and PURPOSE 2 will support a series of
global regulatory filings for lenacapavir for PrEP that will begin
by the end of 2024. Last month, the FDA granted lenacapavir for
PrEP Breakthrough Therapy Designation, which is intended to
expedite the development and review of new drugs that may
demonstrate substantial improvement over available therapy. Also
last month, the FDA granted a rolling review for lenacapavir for
PrEP, a process that allows the FDA to expedite the review of a
drug application by allowing a company to submit sections of the
application for review as they are completed.
Gilead is executing an access strategy, informed by more than
100 global health advocates and organizations, that prioritizes
speed and enables the most efficient paths for the regulatory
review and approval of lenacapavir for PrEP in regions around the
world. Last month, Gilead announced that it had signed
non-exclusive, royalty-free voluntary licensing agreements with six
pharmaceutical companies to manufacture and supply high-quality,
low-cost versions of lenacapavir for 120 high-incidence,
resource-limited countries, which are primarily low- and
lower-middle income countries.
Additionally, Gilead is actively working on additional ways to
support access in upper-middle and high-income countries to
establish fast, efficient pathways to help reach people who need or
want PrEP, including expediting regulatory filings, engagement with
partners and governments, and manufacturing infrastructure
planning. Additionally, in countries with PURPOSE 2 trial sites,
including Argentina, Brazil, Mexico, Peru and the United States,
trial participants are being offered and will be able to stay on
open-label lenacapavir until it is available in their country.
“Gilead recognizes the importance of prevention in ending the
HIV epidemic and is deeply committed to ensuring broad, sustainable
global access to lenacapavir for PrEP, if approved,” said Jared
Baeten, MD, PhD, Senior Vice President, Clinical Development and
Virology Therapeutic Area Head, Gilead Sciences.
Updates on regulatory filings for lenacapavir for PrEP will be
shared as discussions with regulatory bodies progress.
The use of lenacapavir for the prevention of HIV is
investigational and has not been determined to be safe or
efficacious and is not approved anywhere globally.
There is currently no cure for HIV or AIDS.
About the PURPOSE
Program
Gilead’s landmark PURPOSE program is the most comprehensive and
diverse HIV prevention trial program ever conducted. The program
comprises five HIV prevention trials around the world that are
focused on innovation in science, trial design, community
engagement and health equity.
The PURPOSE trials are evaluating the safety and efficacy of an
investigational, twice-yearly injectable medicine, lenacapavir, to
reduce the chance of getting HIV. The Phase 2 and 3 program,
consisting of PURPOSE 1-5, is assessing the potential of
lenacapavir to help a diverse range of people around the world who
could benefit from PrEP.
More information about the PURPOSE program, including individual
trial descriptions, populations and locations, can be found at
www.purposestudies.com.
About
Lenacapavir
Lenacapavir is approved in multiple countries for the treatment
of adults with multi-drug resistant HIV in combination with other
antiretrovirals. The use of lenacapavir for HIV prevention is
investigational and the safety and efficacy of lenacapavir for this
use have not been established.
The multi-stage mechanism of action of lenacapavir is
distinguishable from other currently approved classes of antiviral
agents. While most antivirals act on just one stage of viral
replication, lenacapavir 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 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.
Lenacapavir is being developed as a foundation for potential future
HIV therapies with the goal of offering both long-acting oral and
injectable options with several dosing frequencies, in combination
or as a mono agent, that help address individual needs and
preferences of people and communities affected by HIV.
About Gilead 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 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
one of the leading philanthropic funders of HIV-related programs in
a report released by Funders Concerned About AIDS.
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 and complete
clinical trials in the anticipated timelines or at all, and the
possibility of unfavorable results from ongoing and additional
clinical trials, including those involving lenacapavir (such as
PURPOSE 1 and PURPOSE 2); uncertainties relating to regulatory
applications and related filing and approval timelines, including
regulatory applications for lenacapavir for PrEP, and the risk that
any regulatory approvals, if granted, may be subject to significant
limitations on use or subject to withdrawal or other adverse
actions by the applicable regulatory authority; the possibility
that Gilead may make a strategic decision to discontinue
development of lenacapavir for indications currently under
evaluation and, as a result, lenacapavir may never be successfully
commercialized for such indications; Gilead’s ability to
effectively manage the supply and distribution of lenacapavir,
including through direct supply as well as indirect supply through
the voluntary licensing agreements, and the ability of the parties
to meet potential demand for lenacapavir, in each case, subject to
necessary regulatory approvals; and any assumptions underlying any
of the foregoing. These and other risks, uncertainties and factors
are described in detail in Gilead’s Quarterly Report on Form 10-Q
for the quarter ended September 30, 2024, 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 Truvada,
including Boxed Warning, and lenacapavir are available at
www.gilead.com.
Gilead and the Gilead logo, Truvada, and
Truvada for PrEP 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 X/Twitter
(@Gilead Sciences) and LinkedIn (@Gilead-Sciences).
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version on businesswire.com: https://www.businesswire.com/news/home/20241112740576/en/
Ashleigh Koss, Media public_affairs@gilead.com Jacquie Ross,
Investors investor_relations@gilead.com
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