First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet
Gilead Sciences (GILD) has presented groundbreaking Phase 1 data for its once-yearly lenacapavir formulation for HIV prevention at CROI 2025. The study evaluated two different 5000mg intramuscular formulations in 40 healthy adults, demonstrating sustained plasma concentrations above effective levels for at least 56 weeks.
The trial showed promising results with median trough concentrations at Week 52 (57.0 ng/mL and 65.6 ng/mL) exceeding those observed in previous twice-yearly trials. Both formulations were well-tolerated, with injection site pain being the most common side effect, mostly mild and resolving within a week.
Additional data from the PURPOSE 1 trial revealed that approximately two-thirds of participants preferred twice-yearly lenacapavir injections over daily oral pills at Week 52. The company plans to launch a Phase 3 study for once-yearly lenacapavir in the second half of 2025.
Gilead Sciences (GILD) ha presentato dati innovativi della Fase 1 per la sua formulazione di lenacapavir da somministrare una volta all'anno per la prevenzione dell'HIV al CROI 2025. Lo studio ha valutato due diverse formulazioni intramuscolari da 5000 mg in 40 adulti sani, dimostrando concentrazioni plasmatiche sostenute al di sopra dei livelli efficaci per almeno 56 settimane.
Il trial ha mostrato risultati promettenti con concentrazioni medie al minimo settimanale alla Settimana 52 (57,0 ng/mL e 65,6 ng/mL) superiori a quelle osservate in precedenti trial semestrali. Entrambe le formulazioni sono state ben tollerate, con il dolore nel sito di iniezione come effetto collaterale più comune, per lo più lieve e risolto entro una settimana.
Dati aggiuntivi dal trial PURPOSE 1 hanno rivelato che circa due terzi dei partecipanti preferivano le iniezioni di lenacapavir semestrali rispetto alle pillole orali giornaliere alla Settimana 52. L'azienda prevede di avviare uno studio di Fase 3 per il lenacapavir da somministrare annualmente nella seconda metà del 2025.
Gilead Sciences (GILD) ha presentado datos innovadores de la Fase 1 para su formulación de lenacapavir que se administra una vez al año para la prevención del VIH en CROI 2025. El estudio evaluó dos formulaciones intramusculares de 5000 mg en 40 adultos sanos, demostrando concentraciones plasmáticas sostenidas por encima de los niveles efectivos durante al menos 56 semanas.
El ensayo mostró resultados prometedores con concentraciones medias en el punto más bajo a la Semana 52 (57.0 ng/mL y 65.6 ng/mL) que superaron las observadas en ensayos anteriores de dos veces al año. Ambas formulaciones fueron bien toleradas, siendo el dolor en el sitio de inyección el efecto secundario más común, mayormente leve y que se resolvió en una semana.
Datos adicionales del ensayo PURPOSE 1 revelaron que aproximadamente dos tercios de los participantes preferían las inyecciones de lenacapavir cada seis meses en lugar de las píldoras orales diarias a la Semana 52. La empresa planea lanzar un estudio de Fase 3 para el lenacapavir que se administre una vez al año en la segunda mitad de 2025.
길리어드 사이언스(GILD)는 CROI 2025에서 HIV 예방을 위한 연 1회 투여하는 레나카파비르 제형의 획기적인 1상 데이터를 발표했습니다. 이 연구는 40명의 건강한 성인을 대상으로 두 가지 다른 5000mg 근육 주사 제형을 평가하였으며, 최소 56주 동안 효과적인 수준 이상의 지속적인 혈장 농도를 보여주었습니다.
시험 결과는 52주차에 중간 최저 농도가 (57.0 ng/mL 및 65.6 ng/mL) 이전의 연 2회 시험에서 관찰된 수치를 초과하는 유망한 결과를 보였습니다. 두 가지 제형 모두 잘 견디었으며, 주사 부위 통증이 가장 흔한 부작용으로 나타났고, 대부분 경미하며 일주일 이내에 해결되었습니다.
PURPOSE 1 시험의 추가 데이터에 따르면, 참가자의 약 3분의 2가 52주차에 매일 복용하는 경구용 약물보다 연 2회 레나카파비르 주사를 선호했습니다. 회사는 2025년 하반기에 연 1회 레나카파비르에 대한 3상 연구를 시작할 계획입니다.
Gilead Sciences (GILD) a présenté des données révolutionnaires de Phase 1 pour sa formulation de lenacapavir à administrer une fois par an pour la prévention du VIH lors du CROI 2025. L'étude a évalué deux formulations intramusculaires de 5000 mg chez 40 adultes en bonne santé, démontrant des concentrations plasmatiques soutenues au-dessus des niveaux efficaces pendant au moins 56 semaines.
L'essai a montré des résultats prometteurs avec des concentrations minimales médianes à la Semaine 52 (57,0 ng/mL et 65,6 ng/mL) dépassant celles observées dans des essais précédents semestriels. Les deux formulations ont été bien tolérées, la douleur au site d'injection étant l'effet secondaire le plus courant, généralement léger et résolvant en une semaine.
Des données supplémentaires de l'essai PURPOSE 1 ont révélé qu'environ deux tiers des participants préféraient les injections de lenacapavir semestrielles aux pilules orales quotidiennes à la Semaine 52. L'entreprise prévoit de lancer une étude de Phase 3 pour le lenacapavir à administrer une fois par an dans la seconde moitié de 2025.
Gilead Sciences (GILD) hat auf der CROI 2025 bahnbrechende Phase-1-Daten für seine einmal jährlich zu verabreichende Lenacapavir-Formulierung zur HIV-Prävention vorgestellt. Die Studie bewertete zwei verschiedene intramuskuläre Formulierungen mit 5000 mg bei 40 gesunden Erwachsenen und zeigte, dass die Plasmakonzentrationen über effektiven Werten für mindestens 56 Wochen aufrechterhalten wurden.
Die Studie zeigte vielversprechende Ergebnisse mit medianen Minimalwerten in Woche 52 (57,0 ng/mL und 65,6 ng/mL), die die in früheren halbjährlichen Studien beobachteten Werte übertrafen. Beide Formulierungen wurden gut vertragen, wobei Schmerzen an der Injektionsstelle die häufigste Nebenwirkung darstellten, die in der Regel mild war und innerhalb einer Woche abklang.
Zusätzliche Daten aus der PURPOSE 1-Studie zeigten, dass etwa zwei Drittel der Teilnehmer in Woche 52 die halbjährlichen Lenacapavir-Injektionen den täglichen Tabletten vorzogen. Das Unternehmen plant, in der zweiten Hälfte des Jahres 2025 eine Phase-3-Studie für die einmal jährlich verabreichte Lenacapavir-Formulierung zu starten.
- Phase 1 trial showed sustained effectiveness of once-yearly lenacapavir formulations over 52 weeks
- Strong patient preference for injectable format with ~66% favoring twice-yearly injections over daily pills
- Zero HIV infections reported in both adolescent and adult groups receiving lenacapavir in PURPOSE 1 trial
- Successful expansion of treatment options from twice-yearly to potential once-yearly administration
- High incidence of injection site pain (75-80% of participants)
- Product still requires regulatory approval and is not yet commercially available
- Phase 3 trials haven't started yet, indicating several years before potential market entry
Insights
Gilead's data for once-yearly lenacapavir for HIV prevention represents a significant advancement in long-acting PrEP development. The Phase 1 results show both intramuscular formulations maintained plasma concentrations above effective levels for 52+ weeks, with Week 52 trough concentrations higher than those observed with twice-yearly formulations in Phase 3 trials.
The safety profile appears favorable with mostly mild, transient injection site pain as the primary adverse event. Most notably, this potential once-yearly option addresses a critical market need for improved PrEP adherence – a major barrier to current prevention methods.
Supplemental data from the PURPOSE 1 trial provides compelling evidence of patient preference, with
Lenacapavir's progression to Phase 3 trials in 2H 2025 suggests a commercial launch timeline of approximately 2027-2028, pending positive results. This positions Gilead to potentially capture significant market share in the evolving HIV prevention landscape with a truly differentiated product that addresses fundamental adherence challenges.
The development of a once-yearly PrEP option could fundamentally transform HIV prevention. Current PrEP regimens require either daily pills or more frequent injections, creating significant adherence barriers that limit real-world effectiveness. Lenacapavir's novel mechanism as a capsid inhibitor with multiple-stage viral lifecycle activity provides a high barrier to resistance with no known cross-resistance to existing antiretrovirals.
The pharmacokinetic data is particularly compelling – achieving and maintaining concentrations above the effective threshold for 52+ weeks with median trough concentrations of 57.0-65.6 ng/mL, exceeding the 23.4 ng/mL observed with twice-yearly dosing in Phase 3 trials. This robust drug exposure profile substantially exceeds the minimum effective concentration.
Patient preference data reinforces the clinical value proposition – twice-yearly injections were preferred by approximately two-thirds of study participants over daily oral PrEP, with particularly strong preference among adolescents. This suggests once-yearly administration could drive even greater acceptance.
The safety profile shows primarily mild injection site reactions that resolved within a week, with ice packs demonstrating effectiveness in reducing this discomfort. The lack of new safety signals and comparable profiles between adolescents and adults further derisks the development pathway. The progression to Phase 3 evaluation reflects Gilead's confidence in this transformative approach to HIV prevention.
– Phase 1 Data Indicate Potential for Use of Once-Yearly Lenacapavir for HIV Prevention, with Plans to Launch a Phase 3 Trial in 2H 2025 –
– Also at CROI: New PURPOSE 1 Data Showcasing Preference for Twice-Yearly Lenacapavir vs. Once-Daily Orals and In-Depth Look at Adolescent Pharmacokinetic, Safety and Efficacy Data –
The Phase 1 study data showed that the two different formulations of once-yearly lenacapavir administered via intramuscular injection achieved and maintained plasma concentrations exceeding those associated with HIV prevention efficacy observed in the Phase 3 PURPOSE 1 trial (NCT04994509) and PURPOSE 2 trial (NCT04925752). The previously reported PURPOSE 1 and PURPOSE 2 data showed that twice-yearly subcutaneous lenacapavir demonstrated superiority at reducing HIV infections when compared to background HIV incidence (bHIV) and once-daily oral Truvada® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) in a broad and geographically diverse range of people.
“Gilead is continuing to innovate in our work to develop additional person-centered long-acting injectable and oral options to help people find an HIV prevention choice that is right for them,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world.”
Promising once-yearly lenacapavir for PrEP pharmacokinetic profiles over 52 weeks
The Phase 1 study evaluated the pharmacokinetics, safety and tolerability of two intramuscular single-dose 5000mg lenacapavir formulations. The trial included 40 healthy adults at low risk of HIV acquisition, between the ages of 18 and 55 years, with a body mass index of less than or equal to 35.0 kg/m2.
Lenacapavir plasma concentrations for participants remained above the
Safety data demonstrated both formulations of once-yearly lenacapavir for PrEP were well tolerated, with no new safety signals
Once-yearly lenacapavir is being investigated as an intramuscular injection. This is different from the subcutaneous formulation of lenacapavir, which is being investigated for twice-yearly dosing. The most commonly reported adverse event for both intramuscular formulations studied was injection site pain, which was mostly mild in severity and resolved within 1 week (occurred in
New PrEP modality preference data demonstrate preference for twice-yearly lenacapavir vs. once-daily orals in PURPOSE 1 survey participants
New quantitative survey data and late-breaking qualitative survey data from the PURPOSE 1 trial, evaluating twice-yearly subcutaneous lenacapavir for PrEP among cisgender women in sub-Saharan Africa, were also presented at CROI in two poster sessions. An interim analysis of surveys included 2,561 trial participants’ self-reported preferences for twice-yearly lenacapavir for PrEP injections and once-daily pills, with approximately two-thirds of survey respondents preferring twice-yearly lenacapavir at Week 52 of their trial participation, compared to fewer than one-third of respondents preferring once-daily pills. Additionally, at Week 52, most respondents (
New study population data from PURPOSE 1 show comparable pharmacokinetic and safety profiles for both adolescent and adult trial participants
Additional adolescent-related data from the PURPOSE 1 trial were also presented at CROI yesterday during an oral abstract session and press conference. PURPOSE 1 is the first adult Phase 3 HIV prevention trial to intentionally include adolescents aged 16 and 17 years, and trial enrollment was much higher than in typical adolescent-dedicated studies (124 adolescents, 56 of whom were assigned to the lenacapavir group). The data showed that observed lenacapavir plasma concentrations were comparable between adolescent and adult trial groups, with participants in both groups experiencing the same most common adverse events. There were zero incident HIV infections across the adolescent and adult groups receiving lenacapavir. Given these results, data submitted to regulatory authorities support the potential use of twice-yearly lenacapavir for adolescents who need or want PrEP
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 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. Science Magazine named lenacapavir its 2024 “Breakthrough of the Year.”
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 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, and any potential Phase 3 trials evaluating once-yearly lenacapavir for PrEP); 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; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2024, as filed with the
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/20250311300348/en/
Blair Baumwell, Media
public_affairs@gilead.com
Jacquie Ross, Investors
investor_relations@gilead.com
Source: Gilead Sciences, Inc.
FAQ
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