Gilead’s Twice-Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada® for HIV Prevention

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from an interim analysis of its pivotal, Phase 3 PURPOSE 1 trial indicating that the company’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, demonstrated 100% efficacy for the investigational use of HIV prevention in cisgender women.

PURPOSE 1 met its key efficacy endpoints of superiority of twice-yearly lenacapavir to once-daily oral Truvada^® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) and background HIV incidence (bHIV). Based on these results, the independent Data Monitoring Committee (DMC) recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

“With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We look forward to additional results from the ongoing PURPOSE clinical program and continuing toward our goal of helping to end the HIV epidemic for everyone, everywhere.”

These are the first data generated from Gilead’s landmark PURPOSE program, which is the most comprehensive and diverse HIV prevention trial program ever conducted. The PURPOSE program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement and health equity.

Topline PURPOSE 1 data

PURPOSE 1, a Phase 3, double-blind, randomized study, is evaluating the safety and efficacy of twice-yearly, subcutaneous lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily oral Descovy^® (emtricitabine 200mg and tenofovir alafenamide 25mg; F/TAF) in more than 5,300 cisgender women and adolescent girls aged 16-25 across 25 sites in South Africa and three sites in Uganda. The drugs are being tested in parallel, with one group receiving twice-yearly lenacapavir and one group taking once-daily oral Descovy. Additionally, a third group was assigned once-daily oral Truvada. Study 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.

There were 0 incident cases of HIV infection among women in the lenacapavir group (incidence 0.00 per 100 person-years). The results demonstrated superiority of twice-yearly lenacapavir over bHIV (primary endpoint, incidence 2.41 per 100 person-years) and superiority of twice-yearly lenacapavir over once-daily Truvada (secondary endpoint), with p<0.0001 for both endpoints. In the trial, lenacapavir was generally well-tolerated and no significant or new safety concerns were identified.

HIV incidence in the Descovy group was numerically similar to that in the Truvada group and was not statistically superior to bHIV. Previous clinical trials among cisgender women have commonly found challenges with adherence to daily oral pills for PrEP, and adherence analyses for Descovy and Truvada from PURPOSE 1 are ongoing. In the trial, both Descovy and Truvada were generally well-tolerated and no new safety concerns were identified.

More detailed data from PURPOSE 1 will be presented at a future conference.

“Twice-yearly lenacapavir for PrEP, if approved, could provide a critical new choice for HIV prevention that fits into the lives of many people who could benefit from PrEP around the world—especially cisgender women,” 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 past President of the International AIDS Society. “While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule.”

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.

Additional PURPOSE trials assessing twice-yearly lenacapavir for PrEP are ongoing

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 who have sex with men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. The regulatory filing for lenacapavir for PrEP will include the results of both PURPOSE 1 and PURPOSE 2, if positive, in order to ensure lenacapavir for PrEP can be approved for multiple populations and communities most in need of additional HIV prevention options.

Gilead is committed to partnering with communities that are disproportionately affected by HIV in their respective countries and regions, and community input on the PURPOSE trials has been instrumental in factors ranging from program design to participant recruitment strategies. This kind of collaborative approach will continue to help Gilead implement clinical trials with rigor, innovation and intentional inclusion of communities that have historically been underrepresented in HIV prevention research. It will also help bolster the post-implementation science activities that Gilead will conduct for PURPOSE 1 and future successful trials.

Gilead recognizes the importance of helping to enable access in order for twice-yearly lenacapavir for PrEP, if approved by regulatory authorities, to achieve the broadest impact. In light of today’s milestone and the company’s ongoing commitment to communities affected by HIV, Gilead intends to brief community partners and provide a public statement regarding its planned access approach for high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.

More information about the PURPOSE program, including individual trial descriptions, populations and locations, can be found at www.purposestudies.com.

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

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 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, and the risk that any such 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 Informationfor Descovy and Truvada, including Boxed Warnings, is available at www.gilead.com

Descovy, Descovy for PrEP, Gilead, 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 Twitter (@Gilead Sciences) and LinkedIn, or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.