Gilead's Biannual PrEP Drug Shows 100% Efficacy in HIV Prevention

Gilead Sciences is on the verge of a significant milestone in HIV prevention, as its drug candidate lenacapavir has shown promising results in its PURPOSE 1 phase 3 trial. This trial, which focuses on cisgender women and adolescent girls aged 16 to 25 in South Africa and Uganda, marks the first time an HIV PrEP (pre-exposure prophylaxis) drug candidate has achieved zero infections. Lenacapavir, which is administered subcutaneously twice a year, is already approved by the FDA under the name Sunlenca for use in challenging HIV treatment cases when combined with other antiretroviral medications.

The PURPOSE 1 trial enrolled over 5,300 participants across 28 sites. The participants were divided into groups receiving lenacapavir and those on Gilead’s daily oral PrEP drugs, Descovy and Truvada. Remarkably, none of the more than 2,000 women in the lenacapavir group contracted HIV during the trial. In contrast, the Descovy and Truvada groups recorded infection rates of 2.02 and 1.69 per 100 person-years, respectively.

Linda-Gail Bekker, Ph.D., of the Desmond Tutu HIV Center at the University of Cape Town, emphasized the potential impact of lenacapavir. She noted that the drug could overcome the stigma and discrimination associated with taking daily oral PrEP, thereby increasing adherence due to its twice-yearly dosing schedule.

The trial’s results showed that lenacapavir not only significantly outperformed the background incidence rate of 2.41 per 100 person-years but also demonstrated superiority over Truvada. Consequently, an independent data monitoring committee has advised Gilead to stop the blinded phase of the trial and offer lenacapavir to all participants in an open-label format.

Gilead is also conducting the PURPOSE 2 trial, which evaluates lenacapavir for PrEP among cisgender men who have sex with men, transgender men, and women across several countries, including Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. The results of this trial are expected by late 2024 or early 2025. Gilead plans to combine the findings from both PURPOSE trials for an FDA submission.

If lenacapavir gains approval, it could revolutionize HIV prevention, offering a crucial new option for individuals at risk. This new twice-yearly drug could challenge GSK’s Apretude, which is currently administered every two months, by providing a longer-acting alternative. GSK is working on an every-four-month version set to launch in 2026 and a twice-yearly option expected for a 2027 trial.

The HIV PrEP market is projected to double, potentially reaching £4 billion to £5 billion by 2031, with long-acting injectables comprising 80% of the market value. William Blair analyst Salim Syed predicts that lenacapavir could secure a significant market share, citing its efficacy and potential for improved patient compliance. Lenacapavir’s global peak sales could reach around $3 billion, with the possibility of hitting $4 billion, according to Syed.

The success of lenacapavir elevates the standards for future HIV vaccines, which have faced numerous challenges. After gaining FDA approval for Apretude, GSK has collaborated with the Medicines Patent Pool to make the drug available in resource-limited countries. Similarly, Gilead plans to announce its strategy for expanding lenacapavir access to high-incidence, low-income regions.

Both Gilead and GSK are also advancing ultralong-acting regimens for HIV treatment. Gilead is expected to release a phase 2 update on lenacapavir combined with broadly neutralizing antibodies later this year. Additionally, lenacapavir is being tested with Merck & Co.’s islatravir as a once-weekly oral candidate.