Armed with readouts from the PURPOSE 1 and 2 trials, Gilead Sciences is now gearing up for global regulatory submissions for lenacapavir as a pre-exposure prophylactic option for human immunodeficiency virus.
Gilead Sciences on Thursday released interim results from the Phase III PURPOSE 2 study, demonstrating that an investigational long-acting formulation of its antiretroviral drug lenacapavir drastically reduced the risk of contracting HIV.
PURPOSE 2—which enrolled cisgender men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth—showed that a twice-yearly injection of lenacapavir cut HIV infections by 96% versus its background incidence. Of the 2,180 study participants, only two contracted HIV indicating that 99.9% percent of patients were free of the infection at the time of the interim analysis.
Twice-yearly lenacapavir also bested a daily Truvada (emtricitabine/tenofovir) regimen for HIV pre-exposure prophylaxis (PrEP), according to Gilead.
An independent data monitoring committee confirmed that at the interim analysis PURPOSE 2 achieved its key efficacy endpoint and recommended that the pharma end the blinded phase of the trial and offer open-label lenacapavir to all study participants.
Gilead CEO Daniel O’Day in a statement called Thursday’s results “remarkable,” noting that lenacapavir has “demonstrated the potential to transform the prevention of HIV and help to end the epidemic.” The pharma will “work urgently with regulatory, government, public health and community partners” to make twice-yearly lenacapavir broadly available for PrEP worldwide, if approved, O’Day said.
Gilead is set to start global regulatory filings by the end of the year, with an eye toward initial launch in 2025, according to the company.
Lenacapavir is a selective inhibitor of the HIV-1 capsid function that works by directly binding to the subunits of capsid, disrupting several steps of the virus’ life cycle including its final assembly in and release from an infected host cell. This mechanism of action sets it apart from other antiviral HIV drugs, which target only one stage of the viral replication, according to Gilead. Lenacapavir has so far shown no cross-resistances to other existing drug classes.
Gilead won lenacapavir’s first approval in August 2022, when the European Commission greenlit its twice-yearly use for treating adults with multidrug-resistant HIV. Lenacapavir is marketed as Sunlenca for this indication.
Lenacapavir’s prophylactic use is still investigational and has not yet been cleared by any regulatory authority. To build the PrEP case for the drug, Gilead is running the Phase III PURPOSE program. In June 2024, the pharma released data from PURPOSE 1 touting 100% efficacy for twice-yearly lenacapavir. None of the 2,134 women treated with lenacapavir contracted HIV, as opposed to 16 of the 1,068 women in the Truvada arm, and 39 in the 2,136 women who received Descovy.
