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Gilead Sciences today announced detailed interim analysis results from its pivotal Phase 3 PURPOSE 1 trial.Gilead Sciences' lenacapavir, an HIV capsid inhibitor administered every six months, demonstrated 100% efficacy in preventing HIV in women., compared withOnce-daily oral therapy andThe background incidence of HIV demonstrated significant superiority. Based on these positive results, the independent data monitoring committee recommended that Gilead Sciences unblind the trial early and provide open-label lenacapavir to all participants. According to the press release,If approved, lenacapavir will become the first HIV pre-exposure prophylaxis (PrEP) therapy that requires only two doses per year.The detailed results of the trial were also published simultaneously in The New England Journal of Medicine (NEJM) in.

Globally, there are new additions every yearAbout130Ten ThousandHIVInfection cases.In recent years, research has found that taking antiviral drugs before being infected can reduceAIDSThe risk of viral infection.This preventionAIDSToxicThe therapy for infection is calledPrEPTherapy.The First Approved HIVPrEPThe medication is taken orally once a day.TheTruvada（F/TDF）, ifPressInstructionsTake,Preventing AIDSSignificant effects.From2012Year USAFDAFirst ApprovalF/TDFSince, it is estimated that there have been600Millions of peopleUsePrEP。However,Global women's acceptance, adherence, and persistence regarding PrEP remain limited, highlighting the necessity for developing innovative PrEP medications.

The followingPURPOSE 1It is a double-blind, randomized3Phase Research。Common5338Position16-25General women and adolescent girlsEnrollment, all subjects were tested before enrollmentHIVNegative.SubjectAuthor's Note2：2：1The Proportion，Receive separately once every six monthslenacapavirSubcutaneousInjection,DailyOnceOralAntiviral TherapyDescovy（F/TAF）OrCompared with once-daily oralF/TDF。All subjects received corresponding placebo subcutaneous injections or oral treatments simultaneously during the trial.Due to ethical concerns about the use of placebo in this context, the trial also included unregistered screeners as a control.PrEPObservation Group.

The interim analysis was scheduled to be conducted when 50% of the randomly assigned participants completed at least 52 weeks of follow-up (clinical data cutoff date: May 28, 2024; laboratory data cutoff date: May 29, 2024). The results showed,Among 5,338 subjects, 55 new HIV infections were observed. Among them, the lenacapavir group(n=2134) No subjects were infected(0/100 person-years; 95% CI: 0.00-0.19)，F/TAFGroup（n=2136）In China39Case of infection (2.02/100Person-year;95%  CI：1.44-2.76），F/TDFGroup（n=1068)中有16Case of infection (1.69/100Person-year;95% CI：0.96-2.74）。In screeningPopulation（n=8094) inHIVBackground Incidence RateThenFor2.41/100Person-year (95% CI：1.82-3.19）。

▲LThe HIV infection rate in the enacapavir group was zero (Image source: Reference [2]).

The HIV infection rate in the Lenacapavir group was significantly lower than the background HIV infection rate (InfectionRate ratio = 0.00; 95% CI: 0.00-0.04; P<0.001), also lower thanF/TDFThe HIV infection rate in the group (infection rate ratio = 0.00; 95% CI: 0.00-0.10; P<0.001).F/TAFGroup'sHIVInfectionRate and BackgroundHIVInfectionThe rate showed no significant difference (InfectionRate Ratio=0.84；95% CI：0.55-1.28；P=0.21), andF/TAFGroup andF/TDFBetween groupsHIVInfectionThe rate also showed no significant difference (InfectionRate Ratio=1.20；95% CI：0.67-2.14）。

According to the trial protocol, PURPOSE 1 reached its primary endpoint at the interim analysis, with lenacapavir showing efficacy compared to the background HIV incidence and once-daily oralF/TDFWith superior efficacy,The Independent Data Monitoring Committee recommended that Gilead Sciences stop the double-blind phase of the trial and offer open-label lenacapavir to all participants.As of July 23, more than 840 trial participants had opted to switch to lenacapavir.

Patient adherence analysis shows high adherence and persistence with lenacapavir injections.All groupsInjection compliance is very high, whether it is injection lLenacapavir or placebo, 91.5% of participants received injections on time at week 26, and 92.8% received injections on time at one year. The on-time injection rates were similar across all cohorts, whether receiving lenacapavir or placebo. In contrast,Through the detection of drug levels in the blood of some subjects, it was found that once-daily oral administrationF/TAFAndF/TDFPoor compliance that decreases over time.The low adherence level to once-daily oral PrEP observed in the trial was consistent with what has been reported in previous studies. Notably, in the case-control analysis,F/TAFThe protective effect of antiretroviral drugs is closely related to the medication adherence of the participants.

▲Patients receiving once-daily oral therapy have low medication adherence(Image source: Reference [2])

In terms of safety,lenacapavir、F/TAFAndF/TDFGenerally well tolerated，Not FoundNewSafety issues.LenacapavirIn the group2.8%（n=59) ofSubjectThe patient reported serious adverse events (SAEs），F/TAFGroup as4.0%（n=85），F/TDFGroup as3.3%（n=35）。EachCohortThe frequency of adverse events between the groups was similar.

Lenacapavir (brand name Sunlenca) is a "first-in-class" long-acting HIV capsid inhibitor that can interfere with the assembly and disassembly of HIV viral capsid proteins, acting at multiple stages of the HIV-1 life cycle.Lenacapavir was granted Breakthrough Therapy Designation by the U.S. FDA in May 2019 for the treatment of heavily treatment-experienced HIV-1 patients with multidrug resistance, in combination with other antiretroviral drugs. A previousPhase 2/3 TrialThis indicates that lenacapavir may allow patients to maintain its efficacy with just one injection every six months.

Gilead SciencesExpected by the end of 2024 or early 2025Announce the results of another key trial of the PURPOSE program, PURPOSE 2, which evaluates the efficacy of lenacapavir administered every six months in preventing HIV infection among male and female individuals of different gender orientations.If the results of PURPOSE 1 and PURPOSE 2 are both positive, the regulatory application for lenacapavir as an HIV PrEP therapy will include the results of these two trials., to ensure that lenacapavir can be approved for various populations in greatest need of additional HIV prevention options.

PURPOSE 1 The results of the trial will raise a series of scientific questions,IncludeWill the newly emerged virus affectLenacapavir Resistance? And whether these data can potentially be applied to other high-risk HIV-infected populations? In addition, the press release pointed out,PURPOSE 1 is the first pivotal trial for HIV prevention in adults, including pregnant individuals and adolescents. Therefore, the safety of lenacapavir during pregnancy will be a priority for evaluation.Although many questions remain for researchers to answer, the outstanding effectiveness of lenacapavir in preventing viral infections is indeed a significant advancement in the field of HIV prevention. Let us applaud the scientists, healthcare workers, and participants involved in the drug's development!

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References:

[1] Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024. Retrieved July 24, 2024 from https://www.businesswire.com/news/home/20240724232867/en

[2] Bekker, Linda-Gail et al. “Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.” The New England journal of medicine, 10.1056/NEJMoa2407001. 24 Jul. 2024, DOI:10.1056/NEJMoa2407001

[3] Rochelle P. Walensky et al. “The Real PURPOSE of PrEP — Effectiveness, Not Efficacy” The New England journal of medicine, 24 Jul. 2024, DOI: 10.1056/NEJMe2408591

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