Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024
Gilead Sciences (GILD) announced full efficacy and safety results from its Phase 3 PURPOSE 1 trial for lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor for HIV prevention. Key findings include:
- Zero HIV infections and 100% efficacy in the lenacapavir group
- Superior prevention compared to daily oral Truvada
- High adherence (>90%) to lenacapavir injections
- Generally well-tolerated with no serious injection site reactions
- First adult pivotal HIV prevention trial to include pregnant women and adolescents
If approved, lenacapavir would be the first twice-yearly PrEP option, potentially improving uptake and adherence. Gilead is prioritizing swift access in high-incidence, resource- countries. Results from the PURPOSE 2 trial are expected in late 2024/early 2025.
Gilead Sciences (GILD) ha annunciato i risultati completi di efficacia e sicurezza del suo trial di Fase 3 PURPOSE 1 per lenacapavir, un inibitore del capside dell'HIV-1 somministrato tramite iniezione due volte all'anno per la prevenzione dell'HIV. I risultati chiave includono:
- Zero infezioni da HIV e 100% di efficacia nel gruppo lenacapavir
- Prevenzione superiore rispetto al Truvada orale giornaliero
- Alta aderenza (>90%) alle iniezioni di lenacapavir
- Generalmente ben tollerato, senza reazioni gravi nel sito di iniezione
- Primo trial pivotale per la prevenzione dell'HIV negli adulti ad includere donne in gravidanza e adolescenti
Se approvato, lenacapavir sarebbe la prima opzione di PrEP somministrata due volte all'anno, potenzialmente migliorando l'adesione e la diffusione. Gilead sta dando priorità all'accesso rapido nei paesi a alta incidenza e a risorse limitate. I risultati del trial PURPOSE 2 sono attesi per la fine del 2024/primi del 2025.
Gilead Sciences (GILD) anunció los resultados completos de eficacia y seguridad de su ensayo de Fase 3 PURPOSE 1 para lenacapavir, un inhibidor de cápsides del VIH-1 que se inyecta dos veces al año para la prevención del VIH. Los hallazgos clave incluyen:
- Cero infecciones por VIH y 100% de eficacia en el grupo de lenacapavir
- Prevención superior en comparación con el Truvada oral diario
- Alta adherencia (>90%) a las inyecciones de lenacapavir
- Generalmente bien tolerado, sin reacciones graves en el sitio de inyección
- Primer ensayo pivotal en adultos para la prevención del VIH que incluye a mujeres embarazadas y adolescentes
Si se aprueba, lenacapavir sería la primera opción de PrEP administrada dos veces al año, lo que podría mejorar la adherencia y la aceptación. Gilead está priorizando el acceso rápido en países con alta incidencia y recursos limitados. Se esperan los resultados del ensayo PURPOSE 2 a finales de 2024/principios de 2025.
길리어드 사이언스(GILD)는 HIV 예방을 위한 연 2회 주사형 HIV-1 캡시드 억제제 레나카파비르의 3상 PURPOSE 1 시험의 완전한 효능 및 안전성 결과를 발표했습니다. 주요 결과는 다음과 같습니다:
- 레나카파비르 그룹에서 HIV 감염 제로 및 100%의 효능
- 매일 복용하는 트루바다에 비해 우수한 예방 효과
- 레나카파비르 주사에 대한 높은 순응도(>90%)
- 일반적으로 잘 견뎌내며 심각한 주사 부위 반응이 없음
- 임산부와 청소년을 포함한 첫 번째 성인 중심 HIV 예방 임상 시험
승인될 경우, 레나카파비르는 연 2회 복용 가능한 최초의 PrEP 옵션이 되어, 사용률 및 순응도를 개선할 가능성이 있습니다. 길리어드는 자원이 부족한 고위험 지역에서 빠른 접근을 우선시하고 있습니다. PURPOSE 2 시험의 결과는 2024년 말/2025년 초에 발표될 예정입니다.
Gilead Sciences (GILD) a annoncé les résultats complets d'efficacité et de sécurité de son essai de Phase 3 PURPOSE 1 pour lenacapavir, un inhibiteur de capsides du VIH-1 injectable deux fois par an pour la prévention du VIH. Les principales conclusions comprennent :
- Zéro infection par le VIH et 100% d’efficacité dans le groupe lenacapavir
- Prévention supérieure par rapport au Truvada oral quotidien
- Forte adhésion (>90%) aux injections de lenacapavir
- Généralement bien toléré, sans réactions graves au site d'injection
- Premier essai pivot pour la prévention du VIH chez les adultes à inclure des femmes enceintes et des adolescents
Si approuvé, lenacapavir serait la première option de PrEP administrée deux fois par an, améliorant potentiellement l'utilisation et l'adhésion. Gilead privilégie un accès rapide dans les pays à forte incidence et à ressources limitées. Les résultats de l'essai PURPOSE 2 sont attendus fin 2024/début 2025.
Gilead Sciences (GILD) hat die vollständigen Ergebnisse zur Wirksamkeit und Sicherheit seiner Phase-3-Studie PURPOSE 1 für Lenacapavir bekannt gegeben, ein zweimal jährlich injizierbarer HIV-1-Kapsidhemmer zur HIV-Prävention. Die wichtigsten Ergebnisse umfassen:
- Null HIV-Infektionen und 100% Wirksamkeit in der Lenacapavir-Gruppe
- Überlegene Prävention im Vergleich zu täglich oralem Truvada
- Hohe Adhärenz (>90%) zu Lenacapavir-Injektionen
- Im Allgemeinen gut verträglich, ohne ernsthafte Reaktionen an der Injektionsstelle
- Erste Erwachsenenstudie zur HIV-Prävention, die schwangere Frauen und Jugendliche einbezieht
Wird Lenacapavir genehmigt, wäre es die erste PrEP-Option, die zweimal jährlich verabreicht wird, was die Inanspruchnahme und Adhärenz potenziell verbessern könnte. Gilead priorisiert den schnellen Zugang in Ländern mit hoher Inzidenz und begrenzten Ressourcen. Ergebnisse der Studie PURPOSE 2 werden Ende 2024/Anfang 2025 erwartet.
- Zero HIV infections and 100% efficacy observed for lenacapavir in the trial
- Lenacapavir demonstrated superiority to background HIV incidence and daily Truvada for PrEP
- High adherence (>90%) to twice-yearly lenacapavir injections
- Lenacapavir was generally well-tolerated with no serious injection site reactions
- If approved, lenacapavir would be the first twice-yearly PrEP option, potentially improving uptake and adherence
- Lenacapavir for PrEP is still investigational and not yet approved by regulatory authorities
- Poor adherence observed among participants taking once-daily oral Descovy and Truvada in the trial
- Some participants (0.2%) discontinued lenacapavir due to injection site reactions
Gilead's presentation of the full efficacy and safety results for lenacapavir holds significant potential for revolutionizing HIV prevention, especially in high-incidence, resource-limited environments. The standout result is the demonstrated 100% efficacy of lenacapavir in preventing HIV infections compared to once-daily oral Truvada and background HIV incidence. This is critical since low adherence to daily PrEP regimens remains a challenge.
Lenacapavir's twice-yearly administration can dramatically improve adherence rates, making it a game-changer. With zero reported HIV infections in the lenacapavir group, this drug promises a safer, more effective and user-friendly option, addressing existing gaps in HIV prevention.
Overall, the trial's results underscore lenacapavir's capability to meet and potentially redefine standards in HIV prophylaxis.
For investors, Gilead's promising data on lenacapavir could translate into significant market opportunities. If approved, lenacapavir would be the only twice-yearly PrEP option, meeting a important need for easier adherence. This unique selling point can provide Gilead with a competitive edge in the HIV prevention market, potentially leading to increased market share and revenue.
Moreover, Gilead's commitment to ensuring lenacapavir's swift access in high-incidence, resource-limited countries highlights its strategic focus on global market expansion. This could enhance Gilead's reputation and foster strong partnerships, driving long-term growth.
Overall, the data indicates a positive future trajectory for Gilead in the HIV prevention market.
The financial implications of the successful PURPOSE 1 trial are considerable for Gilead Sciences. The robust efficacy data positions lenacapavir as a strong candidate for regulatory approval, potentially leading to a lucrative revenue stream. The market for HIV prevention is already significant and lenacapavir's twice-yearly dosing could attract individuals who struggle with daily adherence, thus broadening the customer base.
Furthermore, Gilead's strategic emphasis on regulatory approval in high-incidence regions can accelerate market penetration and revenue diversification. Investors should anticipate increased R&D expenditures in the short term, but these are likely to be outweighed by long-term gains from lenacapavir's market success.
In summary, this development should be seen as a net positive for Gilead's financial outlook.
– PURPOSE 1 Data Showed Zero Infections and
– 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 –
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
“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
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
Overall, lenacapavir was highly effective among trial participants, with zero HIV infections observed in the lenacapavir group (0/100 person-years;
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
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:
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;
HIV incidence with Descovy was not different from bHIV (
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;
In the Descovy group, at 26 weeks,
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:
Serious AEs were reported in
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:
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
Four women in the lenacapavir group (
First adult pivotal HIV prevention trial to include pregnant women and adolescents
As a result of strong community input from advocates in
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 (
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
“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.
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
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
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).
View source 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
Source: Gilead Sciences, Inc.
FAQ
What were the main results of Gilead's PURPOSE 1 trial for lenacapavir (GILD)?
When does Gilead (GILD) expect results from the PURPOSE 2 trial for lenacapavir?
How often would lenacapavir be administered for HIV prevention if approved (GILD)?