FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced additional data from its pivotal Phase 3 PURPOSE 2 trial (NCT04925752) providing an overview of the efficacy and safety of 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.
The new data are being presented during an oral abstract session on October 8 at the 5th HIV Research for Prevention Conference (HIVR4P) in Lima, Peru and follow the unblinding of the trial at interim analysis in September, which showed that twice-yearly lenacapavir reduced HIV infections by 96% compared to background HIV incidence (bHIV) and demonstrated superiority to once-daily Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; F/TDF) for HIV prevention as pre-exposure prophylaxis (PrEP).
“These data reinforce that twice-yearly lenacapavir could be a highly effective and potentially game-changing HIV prevention choice that we have long hoped for in our efforts to end the HIV epidemic,” said Colleen Kelley, MD, MPH, Professor of Medicine at Emory University and a PURPOSE 2 Principal Investigator. “PURPOSE 2 was intentionally designed to reflect the lives and locations of many people who are disproportionately affected by HIV around the world by focusing on gender, racial, ethnic and geographic diversity.”
Lenacapavir was highly effective in PURPOSE 2, reducing HIV infections by 96% with two incident cases among 2,179 participants receiving lenacapavir
Lenacapavir was highly effective at reducing infections among trial participants: 99.9% of participants did not acquire HIV in the lenacapavir group, with 2 incident cases among 2,179 participants (0.10/100 person-years, 95% CI, 0.012 to 0.373). The results demonstrated superiority of twice-yearly lenacapavir over bHIV (2.37/100 person-years, 95% CI, 1.649 to 3.417; primary endpoint), with 96% relative risk reduction (IRR 0.04, 95% CI, p<0.0001), compared with 9 incident cases among 1,086 individuals in the Truvada group (0.93/100 person-years, 95% CI, 0.426 to 1.768; secondary endpoint). Additionally, twice-yearly lenacapavir was 89% more effective than once-daily Truvada (IRR 0.11, 95% CI, p=0.00245).
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 3,273 cisgender gay, bisexual, and other men, transgender women, transgender men, and gender nonbinary 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.
This 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.
Lenacapavir was well-tolerated among trial participants with few serious adverse events
Safety and tolerability findings from PURPOSE 2 demonstrated no significant or new safety concerns identified, and lenacapavir was generally well-tolerated.
Aside from injection site reactions (ISRs), the most common adverse events (AEs) observed were rectal chlamydia infection (lenacapavir: 13.2%; Truvada: 11.8%), oropharyngeal gonococcal infection (lenacapavir: 13.0%; Truvada: 10.9%) and rectal gonococcal infection (lenacapavir: 10.7%; Truvada: 9.1%).
Serious AEs were reported in 3.3% of participants in the lenacapavir group, compared to 4.0% in the Truvada group. Frequency of AEs was consistent between study groups.
Few discontinuations due to injection site reactions
Lenacapavir is injected into the subcutaneous layer of fat in the abdomen to form a drug depot, which should 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.
A total of 15,239 lenacapavir and placebo injections were administered during the trial. The most commonly reported ISRs were subcutaneous nodules (lenacapavir: 63.4%; placebo: 39.2%), injection site pain (lenacapavir: 56.4%; placebo: 53.4%) and erythema (lenacapavir: 17.3%; placebo: 19.4%). Twenty-nine people (<1%) across both groups discontinued due to ISRs. ISR incidence, including nodules, decreased with subsequent injections.
High level of diversity among trial participants and geographic regions
The importance of studying HIV prevention across diverse global communities and populations, including gender-diverse populations, was one of the key recommendations from the PURPOSE 2 Global Community Advisory Group (G-CAG) and other community members. As a result, the study enrolled participants from seven countries across four continents and was the first Phase 3 HIV prevention trial to intentionally include transgender men and non-binary individuals.
Among trial participants, 67% were non-White, including 38% Black participants, and 63% were of Hispanic/Latine ethnicity. More than 20% were gender-diverse: 15% were transgender women, 1% were transgender men and 6% were gender non-binary.
Community advocates also stressed the importance of including adolescents and young people in PURPOSE 2, which, along with PURPOSE 1, is the first Phase 3 HIV prevention trial to intentionally include adolescents. About one-third of PURPOSE 2 trial participants were aged 25 years or younger, and the median age of participants was 29.
More detailed data from PURPOSE 2 will be presented at a future conference and in a future publication.
Gilead to begin regulatory filings for lenacapavir for PrEP by the end of 2024 and recently announced voluntary licensing partners to increase access in high-incidence, resource-limited countries
To ensure the results from PURPOSE 1 and PURPOSE 2 help translate into decreased HIV incidence globally if lenacapavir for PrEP is approved, 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. Data from both trials will support a series of global regulatory filings for lenacapavir for PrEP that will begin by the end of 2024.
On October 2, 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 primarily low- and lower-middle income countries. These agreements are just one component of Gilead’s overall global strategy to enable broad, sustainable access to lenacapavir for PrEP, if approved. 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 timely regulatory filings, engagement with partners and governments, and manufacturing planning. This includes the countries with PURPOSE 2 trial sites, including Argentina, Brazil, Mexico, Peru and the United States, where trial participants have been offered and will be able to stay on open-label lenacapavir until it is available in their country.
“The PURPOSE clinical trial program continues to set new standards for innovative science, trial design, community input and intentional recruitment, all coming together to yield stellar results,” said Jared Baeten, MD, PhD, Senior Vice President, Clinical Development and Virology Therapeutic Area Head, Gilead Sciences. “Gilead is committed to employing the same kind of rigorous, thoughtful and collaborative approach to ensure that lenacapavir for PrEP has the most transformative impact possible if approved.”
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 Statement
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 June 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.
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