- 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
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