Gilead submits new drug application to FDA for lenacapavir for HIV prevention

Yesterday, Gilead announced that it has filed a new drug application (NDA) for lenacapavir, a treatment for pre-exposure prophylaxis (PrEP) for HIV infection. The NDA is supported by data provided from the company's Phase 3 Objective 1 and Objective 2 trials. Objective 1 data show that twice-yearly lenacapavir is 100% effective against background HIV incidence (bHIV) in investigational use for HIV prevention in cisgender women, with zero infections in the lenacapavir group. It showed that it showed sex and superiority.¹

In the PURPOSE 2 trial, two HIV infections occurred in the lenacapavir group, and 99.9% of participants in the lenacapavir group remained HIV-free, compared to bHIV in a geographically wide and geographically diverse population of cisgender men. demonstrated a 96% reduction in HIV infections. And people who are gender diverse.¹

What the data shows

The PURPOSE 1 trial included more than 5,300 participants across South Africa and Uganda, and its 100% efficacy rate exceeds the efficacy rate of current standard PrEP options such as Truvada and Descovy.²

An interim analysis conducted by an independent data monitoring committee recommended discontinuing the blinded phase of the trial following these compelling results. Of note, lenacapavir had zero cases of HIV infection among recipients, compared to an incidence rate of 2.41 per 100 person-years in the background HIV prevalence group (bHIV) and once-daily oral Truvada group. It was a target.²

The PURPOSE 2 trial will include cisgender men, transgender men, transgender women, and gender non-binary individuals from Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States, with a partner assigned male at birth. engaged in sexual activity. In an interim analysis, the Independent Data Monitoring Committee (DMC) concluded that the PURPOSE 2 trial showed that twice-yearly lenacapavir for both bHIV (primary endpoint) and once-daily oral Truvada (secondary endpoint) for PrEP It was confirmed that the main efficacy evaluation item of superiority was met. Therefore, the DMC recommended that Gilead discontinue the blinded phase of the study and offer open-label lenacapavir to all participants.³

Study participants were randomly assigned in a 2:1 ratio to lenacapavir and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that placebo groups are unethical. Therefore, this study used bHIV as the primary comparator and Truvada as the secondary comparator.³

Both lenacapavir and Truvada were generally well tolerated, and no significant or new safety concerns were identified.³

Over the past few years, lenacapavir has undergone many evolutions, from FDA regulatory efforts to its use as a treatment for multidrug-resistant HIV patients to its use as a potential PReP tool. Read more here Evolution of lenacapavir in HIV treatmentt.

Gilead said in a statement yesterday that it is working to make lenacapavir more available around the world, especially in areas where it is needed most.

References
1. Gilead has filed a twice-yearly new drug application with the U.S. Food and Drug Administration for lenacapavir for HIV prevention. Gilead press release. Published December 19, 2024. Accessed December 20, 2024.
2. Gilead's twice-yearly lenacapavir demonstrated 100% efficacy and superiority to daily Truvada® in preventing HIV. Gilead press release. Published June 20, 2024. Accessed June 20, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/6/gileads-twiceyearly-lenacapavir-demonstrated-100-efficacy-and-superiority-to-daily-truvada- for HIV prevention
3. Gilead's twice-yearly lenacapavir for HIV prevention reduced HIV infections by 96% and was proven superior to daily Truvada® in a second pivotal Phase 3 trial. Gilead press release. September 12, 2024. Accessed September 12, 2024.
https://www.gilead.com/news-and-press/press-room/press-releases/2024/9/gileads-twiceyearly-lenacapavir-for-hiv-prevention-reduced-hiv-infections-by-96- Demonstrating superiority over important 2nd daily Truvada