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Gilead Sciences today announced its twice-yearly injectableHIVCapsid Inhibitor Lenacapavir for PreventionHIV InfectionThe full results of the second key Phase 3 trial, PURPOSE 2. The analysis shows,Up to 99.9% of participants receiving lenacapavir remained free of HIV infection, and its preventive...HIV InfectionThe effect is superior to the existing once-daily oral therapy.Detailed data were presented at the International Conference on AIDS Virus Infection Drug Treatment and will be published in The New England Journal of Medicine. Last month,The U.S. FDA Granted Lenacapavir forHIV InfectionBreakthrough Therapy Designation for Pre-Exposure Prophylaxis (PrEP). The company anticipates initiating a series of global regulatory submissions for lenacapavir in PrEP before the end of this year.

About 1.3 million new HIV infection cases are reported globally each year. In recent years, research has found that taking antiviral drugs before being exposed to the virus can reduce the risk of HIV infection. This preventive treatment for HIV infection is called PrEP therapy. The first approved HIV PrEP drug is...Developed by Gilead Sciences, Inc.Truvada, if taken daily as directed, is highly effective in preventing HIV.Although daily oral PrEP therapy can almost 100% preventHIV InfectionHowever, due to factors such as the cost of medication and the stigma associated with taking HIV-related drugs, many people struggle to adhere to daily medication. The actual effectiveness of oral PrEP therapy is far lower than its theoretical value.Therefore, there is a significant demand for the development of a long-acting PrEP therapy that can enhance medication adherence.

PURPOSE 2 is a randomized, double-blind, multicenter Phase 3 study designed to evaluate in 3,271 subjects, against backgroundHIVIncidence (bHIV) and the safety and efficacy of lenacapavir administered subcutaneously twice a year as PrEP compared to once-daily oral Truvada. The full trial results announced are as follows:

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Subjects Showed High Adherence to Lenacapavir Injection

Subject AcceptancePlacebo andLenacapavir Injection Has High Compliance:At Week 26, 91.0% of participants received injections on schedule; at one year into the trial, 92.8% of participants received injections on schedule.The on-time injection rates (within 28 weeks after the previous injection) were similar between the two cohorts, regardless of whether they received lenacapavir or placebo injections.

Compared with the background HIV incidence rate, lenacapavir reduced the HIV infection rate by 96%.

Lenacapavir can effectively reduce theHIVInfection Rate: 99.9% of Lenacapavir Group Subjects Were Not InfectedHIVPURPOSEDespite higher levels of participant-reported sexual behavior, chemsex, and sexually transmitted infections, there were only 2 new cases (0.10/100 person-years, 95% CI: 0.01 to 0.37) among 2179 participants. The analysis showed that the trial met its primary endpoint.Lenacapavir Twice a Year for PreventionHIVInfection with bHIV(2.37/100 person-years, 95% CI: 1.65 to 3.42),Relative risk reduction of 96% (Incidence Rate Ratio [IRR]: 0.04; 95% CI: 0.01 to 0.18; p<0.0001).In addition,Compared with taking Truvada once daily, lenacapavir reducesHIVThe risk of infection is 89% higher.(IRR: 0.11; 95% CI: 0.02 to 0.51; p=0.00245).

Two InfectionsHIVThe lenacapavir plasma concentrations in the subjects were within the overall drug concentration range of a representative subgroup of subjects with pre-specified, plasma level-tested. The trial data confirmed,Two Subjects Were Infected With HIV After First Injection of Lenacapavir and Before Second Injection, and both subjects were using the standardHIVTesting for diagnosis. Importantly, based on retrospective HIV-1 RNA viral load testing of previous follow-up samples, the diagnosis of AIDS infection for these two individuals was not delayed. The field of HIV PrEP, particularly, is concerned about infections in users of long-acting PrEP.HIVThe possibility of delayed diagnosis.

Adherence to Truvada was initially high but declined over time.

The trial measured adherence to Truvada by randomly testing tenofovir diphosphate in participants' blood samples, and found that adherence was initially high but decreased over time:At Week 8, 82% of participants had tenofovir diphosphate levels consistent with high adherence (four or more tablets per week), decreasing to 67% at Week 26 and 62% at one year.

Truvada Group Experienced 9 IncidentsHIVInfection incidents, all subjects had very low or no compliance.

Among the 1086 people in the Truvada group, 9 cases occurred (0.93/100 person-years, 95% CI: 0.43 to 1.77). The data indicates,These 9 subjects had either very low or no adherence to Truvada, or had stopped taking the drug more than 10 days before diagnosis.Among these 9 subjects, 2 had lower levels of tenofovir diphosphate, 6 had levels below the limit of detection, and 1 stopped taking Truvada.

PURPOSE 2 is the second pivotal Phase 3 trial of lenacapavir. Announced in June 2024.PURPOSE 1Key Phase 3 trial results show that lenacapavir in womenHIV InfectionShowed 100% efficacy for preventive use, and the trial was unblinded early due to reaching the key efficacy endpoint.Gilead Expects Data from PURPOSE 1 and PURPOSE 2 Trials to Support Upcoming Regulatory Filings.

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

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References:

[1] Gilead Presents Full PURPOSE 2 Data Results for Twice-Yearly Lenacapavir for HIV Prevention at HIV Glasgow. Retrieved November 13, 2024 from https://www.businesswire.com/news/home/20241112740576/en

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