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Adherence and efficacy were both higher in patients with HIV who took twice-yearly lenacapavir compared to those on oral preexposure prophylaxis medication.
Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, demonstrated 100% efficacy, no infections, and superiority compared to background HIV incidence in cisgender women, according to results published in The New England Journal of Medicine and a news release from Gilead.1,2
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The results from the pivotal phase 3 PURPOSE 1 (NCT04994509) trial indicates the safety, efficacy, and tolerability of twice-yearly lenacapavir injections. The data was presented at a late-breaking session at the 25th International AIDS Conference in Munich, Germany.2
“These stellar results show that twice-yearly lenacapavir for PrEP, if approved, could offer a highly effective, tolerable and discreet choice that could potentially improve PrEP uptake and persistence, helping us to reduce HIV in cisgender women globally,” Linda-Gail Bekker, former president of the International AIDS Society, said in the news release.2
“PURPOSE 1 also sets a new standard for person-centered HIV prevention trials, demonstrating what can happen when a thoughtful scientific and community-focused trial design, a promising drug candidate and an inclusive trial implementation plan come together,” Bekker continued.2
Cisgender women account for half of new HIV infections that occur worldwide each year. Preexposure prophylaxis (PrEP) medication, such as daily oral emtricitabine-tenofovir alafenamide (F/TAF) or emtricitabine–tenofovir disoproxil fumarate (F/TDF), is effective if taken consistently. However, many cisgender women around the world have limited uptake and adherence to PrEP medication.1
The PURPOSE 1 trial included a total of 5338 participants, who were randomized and received at least one dose of a trial drug or a placebo. There were 55 incident HIV infections observed, with none occurring in the lenacapavir cohort.1
Lenacapavir was found to reduce HIV incidence by 100% as compared with background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P < 0.001). This can be compared to background HIV incidence, which was 2.41/100 person-years (95% CI, P < 0.0001).1
Additionally, adherence to both lenacapavir and placebo injections were high, with 91.5% of all trial participants receiving on-time injections at week 26, and 92.8% of participants receiving on-time injections at the 1-year mark.1,2
Contrastingly, adherence to daily oral F/TAF and F/TDF was poor. This finding was consistent with previously published literature that has reported low adherence to daily oral F/TDF and a correspondingly low effectiveness in women across geographic areas.1
Trial Name: Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1)
Trial Sponsor: Gilead Sciences
ClinicalTrials.gov ID: NCT04994509
Estimated Trial Completion: July 2027
This could be explained by multiple reasons, including stigma, inaccurate perception of the likelihood of the acquisition of an HIV infection, or the dislike of or lack of experience with daily, consistent pill taking, the investigators postulated.1
“A twice yearly PrEP choice could overcome challenges with respect to adherence and persistence and result in substantial protection against HIV infection for women worldwide,” the investigators of the PURPOSE 1 trial wrote.1
Although lenacapavir is not yet approved by the FDA for use in patients, Gilead is developing a strategy that “prioritizes speed and enables the most efficient path” for regulatory approval in countries that shoulder the brunt of the disease burden.3
Gilead is exploring frameworks that can facilitate quick access to target populations and countries. These include the European Medicines Agency’s EU Medicines for All, and the World Health Organization’s prequalification and collaborative review procedures.3
The company plans to include both PURPOSE 1 and, if there are positive results, PURPOSE 2 in the regulatory filing for PrEP. PURPOSE 2 is analyzing twice-yearly lanacapavir for PrEP among different groups, including cisgender men, transgender women, transgender men and gender non-binary individuals.3
Through Gilead’s discussions with the HIV community, they’ve determined key priorities for lenacapavir’s eventual rollout, including developing enough of the drug to meet demand, selling the drug at an affordable price point that can enable widespread availability, and coordinating with stakeholders on the ground.3
Gilead expects results from the PURPOSE 2 trial in late 2024 or early 2025.2
