Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024

FOSTER CITY, Calif.--(BUSINESS WIRE)-- 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 25^th International AIDS Conference (AIDS 2024) in Munich, Germany and were published today in TheNew 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 Descovywere 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 Informationfor 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).