Lenacapavir Highly Effective in Preventing HIV

New data from the phase 3 PURPOSE 2 trial (NCT04925752) were presented at the 5th HIV Research for Prevention Conference held in Lima, Peru, that could indicate significant efficacy of lenacapavir in preventing HIV. Early results show a 96% rate of reduced infections.¹

The phase 3 PURPOSE 2 trial is assessing lenacapavir as a pre-exposure prophylaxis (PrEP) medicine to reduce the chance of getting HIV through sex, comparing it when taken twice per year as PrEP with expected background HIV incidence (bHIV) and oral emtricitabine/tenofovir disoproxil fumarate (F/TDF; Truvada; Gilead) taken daily.² Lenacapavir is given to patients every 6 months through an injection and compared with other participants in the trial receiving daily . The trial will last up to 3 years as it evaluates the efficacy of the treatment. Participants of the trial could not have HIV when they enrolled.

All 3273 participants were 16 years or older and were cisgender gay, bisexual, as well as other men; transgender men; transgender women; and gender nonbinary who had sex with men. The trial was conducted in multiple countries throughout the world, including the US, Brazil, Thailand, Mexico, and South Africa. The study population included 67% who were non-White, which included 63% of participants who were of Hispanic or Latino ethnicity and 38% who identified as Black. All participants were separated into a 2:1 ratio to be assigned into 2 groups: either lenacapavir or F/TDF.

The PURPOSE 2 trial, consisting mostly of individuals who have sex with men, revealed promising results for lenacapavir's use as PrEP | Image credit: Krakenimages.com - stock.adobe.com

The findings were presented as an oral abstract during the conference. Early findings included the efficacy of the treatment, which showed that 99.9% of participants on lenacapavir did not acquire HIV, with only 2 cases overall among 2179 participants (95% CI, 0.012-0.373). The treatment was superior to that of bHIV (95% CI, 1.649-3.417) as it had a 96% relative risk reduction. In comparison, the F/TDF group had 9 incident cases among 1086 individuals and lenacapavir taken twice per year was 89% more effective.

There were no new safety concerns found in patients taking lenacapavir. The most common adverse events included rectal chlamydia infection (13.2%), oropharyngeal gonococcal infection (13.0%), and rectal gonococcal infection (10.7%). All of these were higher in incidence compared with patients who received F/TDF (11.8%, 10.9%, and 9.1% respectively). Less than 1% of the population discontinued the medication due to injection site reactions.

These results are a promising follow-up to the PURPOSE 1 trial results that were released in June.³ These initial results found that lenacapavir was able to prevent all infections in participants using the treatment, a trial made up of adolescent and young cisgender women. In an interview with The American Journal of Managed Care^®, Jared Baeten, MD, PhD, vice president of HIV clinical development at Gilead Sciences, said that Gilead had been working hard in the PURPOSE program to gather information about the efficacy and safety of lenacapavir in populations around the world to change lenacapavir from investigational for PrEP to more widespread use.

When asked how the biyearly injection could be a benefit, Baeten said, “It could potentially remove some of the stigma and discrimination of taking medicines for HIV prevention. It certainly removes having to have a pill bottle in your purse or your medicine cabinet or your bedside table that someone could find. And that really could allow people to be able to take potentially effective HIV prevention on a more regular basis and with greater persistence.”

Lenacapavir continues to be looked into in separate PURPOSE trials, including PURPOSE 3, which is evaluating HIV prevention in cisgender adult women, and PURPOSE 4, which is evaluating the efficacy of HIV prevention in people who inject drugs. These results could help to determine availability of lenacapavir as PrEP in the future.²

References

1. Gilead presents additional efficacy, safety and demographic data from PURPOSE 2 trial at 5th HIV Research for Prevention Conference. News release. Gilead; October 7, 2024. Accessed October 9, 2024. https://www.gilead.com/news/news-details/2024/gilead-presents-additional-efficacy-safety-and-demographic-data-from-purpose-2-trial-at-5th-hiv-research-for-prevention-conference

2. PURPOSE 2. Purpose Studies. Accessed October 9, 2024. https://www.purposestudies.com/purpose2/about-the-study/

3. Bonavitacola J. Lenacapavir offers future method of HIV prevention after stellar trial results. AJMC^®. June 27, 2024. Accessed October 9, 2024. https://www.ajmc.com/view/lenocapovir-offers-future-method-of-hiv-prevention-after-stellar-trial-results