– PURPOSE 1 Data Showed Zero Infections and
100% Efficacy and Superiority of Lenacapavir to Background HIV
Incidence and Daily Truvada® for PrEP –
– If Approved, Lenacapavir Would be the
First and Only Twice-Yearly PrEP Choice and Could Address Critical
Gaps in Uptake and Adherence for Individuals Who Need or Want PrEP
–
– Gilead Commits to Prioritizing Swift
Access and Enabling Efficient Paths for Regulatory Approval of
Lenacapavir for PrEP in High-Incidence, Resource-Limited Countries
–
Gilead Sciences, Inc. (Nasdaq: GILD) today announced full
efficacy and safety results from its pivotal, Phase 3 PURPOSE 1
trial. Detailed data from the trial’s interim analysis announced in
June showed that lenacapavir, the company’s twice-yearly injectable
HIV-1 capsid inhibitor, demonstrated zero infections, 100% efficacy
and superiority to background HIV incidence for the investigational
use of HIV prevention in cisgender women (women assigned female at
birth). Lenacapavir also demonstrated superior prevention of HIV
infections when compared with once-daily oral Truvada
(emtricitabine 200mg and tenofovir disoproxil fumarate 300mg;
F/TDF).
The new data provide details on the efficacy, safety and
tolerability of twice-yearly lenacapavir injections; drug adherence
among trial participants, including poor levels of adherence to
daily oral pre-exposure prophylaxis (PrEP) and high levels of
adherence to lenacapavir; and demographic and behavioral
characteristics of trial participants, including pregnant women and
adolescents.
The data are being presented at a special late-breaking session
at the 25th International AIDS Conference (AIDS 2024) in Munich,
Germany and were published today in The New England Journal of
Medicine.
“These stellar results show that twice-yearly lenacapavir for
PrEP, if approved, could offer a highly effective, tolerable and
discreet choice that could potentially improve PrEP uptake and
persistence, helping us to reduce HIV in cisgender women globally,”
said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD,
Director of the Desmond Tutu HIV Center at the University of Cape
Town, South Africa, and former President of the International AIDS
Society. “PURPOSE 1 also sets a new standard for person-centered
HIV prevention trials, demonstrating what can happen when a
thoughtful scientific and community-focused trial design, a
promising drug candidate and an inclusive trial implementation plan
come together.”
To ensure the groundbreaking data from PURPOSE 1 translates into
decreased HIV incidence globally, Gilead is building an access
strategy that prioritizes speed and enables the most efficient path
for the regulatory approval of twice-yearly lenacapavir for PrEP in
countries that account for most of the global disease burden. For
more information, see Gilead’s statement on access planning in
high-incidence, resource-limited countries for lenacapavir for
PrEP.
Zero infections and 100% efficacy observed for lenacapavir at
interim analysis
Overall, lenacapavir was highly effective among trial
participants, with zero HIV infections observed in the lenacapavir
group (0/100 person-years; 95% CI, 0.00 to 0.19) compared to
background HIV incidence (bHIV) (2.41/100 person-years; 95% CI,
1.82 to 3.19), translating to a 100% reduction in HIV infections.
Additionally, compared to once-daily Truvada, lenacapavir reduced
HIV incidence by 100%, a result that was statistically superior
(IRR 0; 95% CI, p<0.0001).
Per trial protocol, because PURPOSE 1 met its key efficacy
endpoints of superiority of twice-yearly lenacapavir to bHIV and
once-daily oral Truvada at interim analysis, the independent Data
Monitoring Committee recommended that Gilead stop the blinded phase
of the trial and offer open-label lenacapavir to all participants.
As of July 23, more than 840 trial participants have already opted
to switch to lenacapavir.
PURPOSE 1 (NCT04994509) is evaluating the safety and efficacy of
twice-yearly, subcutaneous lenacapavir for PrEP and once-daily oral
Descovy® (emtricitabine 200mg and tenofovir alafenamide 25mg;
F/TAF) for the investigational use of HIV prevention in cisgender
women. Data from the Phase 3, double-blind, active-controlled,
multicenter, randomized trial were collected from 5,345
HIV-negative, cisgender adolescent girls and young women aged 16-26
at 25 sites in South Africa and three sites in Uganda. Lenacapavir
and Descovy were tested in parallel for HIV prevention, with one
group receiving twice-yearly injectable lenacapavir and one group
taking once-daily oral Descovy. Additionally, a third group was
assigned once-daily oral Truvada. Baseline demographics and
characteristics were balanced across all groups. Trial participants
were randomized in a 2:2:1 ratio to lenacapavir, Descovy 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. Most of the
participants (80.5%) reported prior HIV testing. A small minority
(6.3%) reported no prior use of PrEP.
High adherence to and persistence of twice-yearly injectable
lenacapavir
Adherence to lenacapavir and to placebo injections included in
the oral PrEP study groups was high: 91.5% 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 all study groups, whether receiving lenacapavir or placebo
injections.
Incident HIV infections in Descovy and Truvada trial
groups
Sixteen incident HIV cases among 1,068 women were observed in
the Truvada group (1.69/100 person-years; 95% CI, 0.96 to 2.74) and
39 incident HIV cases among 2,136 women were observed in the
Descovy group (2.02/100 person-years; 95% CI, 1.44 to 2.76).
HIV incidence with Descovy was not different from bHIV (IRR
0.84; 95% CI, 0.55 to 1.28; p=0.21) in the primary efficacy
analysis and no evidence of difference was observed compared to
Truvada (IRR 1.20; 95% CI, 0.67 to 2.14) in the secondary efficacy
analysis.
Poor adherence among women taking once-daily oral Descovy and
Truvada
Adherence to once-daily oral Descovy and Truvada, measured
through detection of tenofovir diphosphate in blood samples from a
subset of patients, was low and declined over time. These adherence
levels are consistent with prior reports of low adherence of daily
oral PrEP among cohorts of cisgender women, especially among
younger women, across geographies.
HIV protection was strongly associated with adherence to Descovy
in the case-control analysis. Most participants with incident HIV
infection had low or no detection of tenofovir diphosphate
(Descovy, 34 of 37; Truvada, 13 of 14; 2 participants in each group
missing data). Within the Descovy group, those with medium (defined
as 2-3 doses per week) or high (defined as four or more doses per
week) adherence had significantly lower odds of acquiring HIV
infection compared to those with low (defined as fewer than two
doses per week) adherence (odds ratio 0.11; 95% CI, 0.012 to 0.49;
p=0.0006).
In the Descovy group, at 26 weeks, 30.2% of trial participants
had high or medium adherence to the drug, and 69.8% had low
adherence. At one year in the Descovy group, 15.9% of trial
participants had high or medium adherence, and 84.1% had low
adherence. In the Truvada group, at 26 weeks, 10.9% of trial
participants had high or medium adherence, and 89.1% had low
adherence. At one year in the Truvada group, 7.0% of trial
participants had high or medium adherence and 93.0% had low
adherence.
Lenacapavir and Descovy were generally well tolerated
There were no new safety concerns identified, and lenacapavir,
Descovy and Truvada were generally well tolerated.
For lenacapavir and Descovy, aside from injection site reactions
(ISRs), the most common adverse events (AEs) observed were headache
(lenacapavir: 13.3%; Descovy: 16.5%), urinary tract infection
(lenacapavir: 14.4%; Descovy 14.3%), genitourinary chlamydia
infection (lenacapavir: 14.0%; Descovy 14.8%) and nausea
(lenacapavir: 6.7%; Descovy: 10.9%).
Serious AEs were reported in 2.8% (n=59) of participants in the
lenacapavir group, compared to 4.0% (n=85) in the Descovy group and
3.3% (n=35) in the Truvada group. Frequency of AEs was similar
across study groups.
No serious injection site reactions
A total of 25,329 injections were administered: 10,154 in 2,138
participants assigned to the lenacapavir group, and 15,175 in 3,206
participants receiving placebo injections in the Descovy and
Truvada groups. ISRs related to the study drug or injection
procedures were the most common AEs observed (lenacapavir: 68.8%;
placebo: 34.9%), and there were no serious ISRs among participants
receiving lenacapavir or placebo injections.
Lenacapavir is injected into the subcutaneous layer of fat in
the abdomen to form a drug depot, which will get smaller and
resolve, or reduce in size substantially, prior to the next
lenacapavir injection. The drug depot may be palpable as a bump or
nodule but is usually not visible. About 64% (63.8%) of women in
the lenacapavir group experienced nodules compared to 16.6% who
received placebo injections. ISR incidence, including nodules,
decreased with subsequent injections.
Four women in the lenacapavir group (0.2%) discontinued study
drug due to ISRs, compared to zero women who discontinued due to
ISRs on placebo.
First adult pivotal HIV prevention trial to include pregnant
women and adolescents
As a result of strong community input from advocates in South
Africa and Uganda, PURPOSE 1 is the first HIV prevention trial to
intentionally include pregnant and lactating women. There were 510
pregnancies among 487 participants: 193 among women in the
lenacapavir group, with zero HIV infections; 219 among women in the
Descovy group, with four HIV infections; and 98 among women in the
Truvada group, with one HIV infection. At the time of interim
analysis, 54.3% of pregnancies were completed and 45.7% were
ongoing. Available pregnancy outcomes were similar to those
expected for the population.
Community advocates also stressed the importance of including
adolescents and young people in PURPOSE 1. The median age of all
trial participants was 21 years, and 124 (2.3%) participants were
under 18 years.
PURPOSE 2 results expected late 2024/early 2025
Gilead expects results in late 2024/early 2025 from the
program’s other pivotal trial, PURPOSE 2, which is assessing
twice-yearly lenacapavir for PrEP among cisgender men, transgender
men, transgender women and gender non-binary individuals in
Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the
United States who have sex with partners assigned male at birth.
The regulatory filing for lenacapavir for PrEP will include the
results of both PURPOSE 1 and PURPOSE 2, if positive, to ensure
lenacapavir for PrEP can be approved for multiple populations and
communities most in need of additional HIV prevention options.
“As the most comprehensive and diverse HIV prevention trial
program ever conducted, the PURPOSE program embodies both the
scientific and person-centered innovations that Gilead believes are
critical to help end the HIV epidemic for everyone, everywhere,”
said Jared Baeten, MD, PhD, Senior Vice President, Clinical
Development and HIV Franchise Head, Gilead Sciences. “As the only
twice-yearly choice for HIV prevention, lenacapavir for PrEP could
provide a critical new option for people who need or want PrEP
around the world.”
The use of lenacapavir and the use of Descovy for the prevention
of HIV in cisgender women are investigational and have not been
determined to be safe or efficacious and are 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.
U.S. Indication for Descovy for
PrEP®
DESCOVY for PrEP is indicated in at-risk adults and adolescents
(≥35 kg) to reduce the risk of sexually acquired HIV-1 infection,
excluding individuals at risk from receptive vaginal sex.
HIV-1–negative status must be confirmed immediately prior to
initiation.
Limitation of Use: DESCOVY FOR PrEP is not indicated in
individuals at risk of HIV-1 from receptive vaginal sex because
effectiveness in this population has not been evaluated by the U.S.
FDA.
U.S. Important Safety Information for
Descovy for PrEP
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY
FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT
ACUTE EXACERBATION OF HEPATITIS B
- DESCOVY FOR PrEP must be prescribed only to individuals
confirmed to be HIV negative immediately prior to initiation and at
least every 3 months during use. Drug-resistant HIV-1 variants have
been identified with use of emtricitabine/tenofovir disoproxil
fumarate (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1
infection. Do not initiate if signs or symptoms of acute HIV-1
infection are present unless HIV-negative status is confirmed
- Severe acute exacerbations of hepatitis B have been reported in
individuals infected with hepatitis B virus (HBV) who discontinued
products containing FTC and/or TDF and may occur with
discontinuation of DESCOVY. Closely monitor hepatic function with
both clinical and laboratory follow-up for at least several months
in individuals with HBV who discontinue DESCOVY. If appropriate,
anti-hepatitis B therapy may be warranted
Contraindication
- DESCOVY FOR PrEP is contraindicated in individuals with unknown
or positive HIV status
Warnings and precautions
- Comprehensive management to reduce risks:
- Use DESCOVY FOR PrEP to reduce the risk of HIV-1 infection as
part of a comprehensive strategy that includes adherence to daily
dosing and safer sex practices, including condoms, to reduce the
risk of sexually transmitted infections (STIs)
- HIV-1 risk factors: Behavioral, biological, or
epidemiologic HIV-1 risk factors may include, but are not limited
to: condomless sex, past or current STIs, self-identified HIV risk,
having sexual partners of unknown HIV-1 viremic status, or sexual
activity in a high-prevalence area or network
- Reduce STI risk: Counsel on the use of STI prevention
measures (e.g., consistent and correct condom use, knowledge of
partner’s HIV-1 viremic status, regular testing for STIs)
- Reduce potential for drug resistance: Only prescribe
DESCOVY FOR PrEP to individuals confirmed to be HIV negative
immediately prior to initiation, at least every 3 months while
taking DESCOVY, and upon an STI diagnosis. HIV-1 resistance
substitutions may emerge in individuals with undetected HIV-1
infection who are taking only DESCOVY because DESCOVY alone is not
a complete regimen for treating HIV-1
- Some HIV tests may not detect acute HIV infection. Prior to
initiating DESCOVY FOR PrEP, ask individuals about potential recent
exposure events. If recent (<1 month) exposures are reported or
suspected, or symptoms of acute HIV infection (e.g., fever,
fatigue, myalgia, skin rash) are present, confirm HIV-negative
status with a test approved by the FDA for use in the diagnosis of
acute HIV infection
- If HIV-1 infection is suspected or if symptoms of acute
infection are present while taking DESCOVY FOR PrEP, convert the
DESCOVY FOR PrEP regimen to a complete HIV treatment regimen until
HIV-negative status is confirmed by a test approved by the FDA for
use in the diagnosis of acute HIV infection
- Counsel on adherence: Counsel individuals to strictly
adhere to daily dosing, as efficacy is strongly correlated with
adherence. Some individuals, such as adolescents, may benefit from
more frequent visits and counseling
- 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 DESCOVY in individuals with estimated creatinine clearance
(CrCl) <30 mL/min. Individuals with impaired renal function
and/or taking nephrotoxic agents (including NSAIDs) are at
increased risk of renal-related adverse reactions. Discontinue
DESCOVY in individuals who develop clinically significant decreases
in renal function or evidence of Fanconi syndrome. Monitor renal
function in all individuals (see Dosage and Administration
section)
- Lactic acidosis and severe hepatomegaly with steatosis:
Fatal cases have been reported with the use of nucleoside analogs,
including FTC and TDF. Discontinue use 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 (≥2%) in the DESCOVY FOR
PrEP clinical trial were diarrhea, nausea, headache, fatigue, and
abdominal pain
Drug interactions
- Prescribing information: Consult the full Prescribing
Information for DESCOVY for more information, warnings, and
potentially significant drug interactions, including clinical
comments
- Metabolism: Drugs that inhibit P-gp can increase the
concentrations of tenofovir alafenamide (TAF), a component of
DESCOVY. Drugs that induce P-gp can decrease the concentrations of
TAF, which may lead to loss of efficacy
- Drugs affecting renal function: Coadministration of
DESCOVY 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: One tablet taken once daily with or without
food
- HIV screening: Test for HIV-1 infection immediately
prior to initiating, at least every 3 months during use, and upon
diagnosis of an STI (see Warnings and Precautions section)
- HBV screening: Test for HBV infection prior to or when
initiating DESCOVY
- Renal impairment and monitoring: Not recommended in
individuals with creatinine clearance (CrCl) <30 mL/min. Prior
to or when initiating DESCOVY, and during use on a clinically
appropriate schedule, assess serum creatinine, CrCl, urine glucose,
and urine protein in all individuals. In individuals with chronic
kidney disease, assess serum phosphorus
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.
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 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 Descovy, Truvada and
lenacapavir (such as PURPOSE 1 and PURPOSE 2); uncertainties
relating to regulatory applications and related filing and approval
timelines, including any regulatory applications for lenacapavir
for PrEP, and the risk that any regulatory approvals, if granted,
may be subject to significant limitations on use; the possibility
that Gilead may make a strategic decision to discontinue
development of Descovy and lenacapavir for indications currently
under evaluation and, as a result, Descovy and lenacapavir may
never be successfully commercialized for such indications; 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 March 31, 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 Descovy
and Truvada, including Boxed Warnings, and lenacapavir are
available at www.gilead.com.
Descovy, Descovy for PrEP, 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/20240724232867/en/
Ashleigh Koss, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
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