Gilead plans to go straight to Phase III studies for once-yearly lenacapavir, while GSK and ViiV will push forward with their long-acting antivirals after touting positive early-stage results.
Long-acting HIV therapies took center stage at the ongoing 2025 Conference on Retroviruses and Opportunistic Infections in San Francsico, with Gilead and GSK and development partner ViiV Healthcare touting promising data for their respective assets and setting the stage for advanced development.
Gilead debuted Phase I findings for two novel formulations of lenacapavir, which could potentially allow once-yearly injections for the prevention of HIV. Data, published simultaneously in The Lancet, showed that once-yearly pre-exposure prophylaxis (PrEP) led to median plasma lenacapavir concentrations higher than what was needed to show efficacy in Phase III trials that treated patients twice yearly.
A readout from the PURPOSE 1 study, released in June 2024, found that twice-yearly lenacapavir could prevent HIV in 100% of immunized cisgender women, while PURPOSE 2 found a 96% reduction in the risk of HIV in cisgender men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth.
On the strength of these Phase I findings, Gilead plans to skip Phase II and go straight to Phase III development for once-year pre-exposure prophylaxis (PrEP) with lenacapavir. A study is set to launch later this year.
“Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world,” Jared Baeten, Gilead’s Virology Therapeutic Area head, said in a statement.
Also on Tuesday, GSK and ViiV unveiled data for their long-acting antiviral VH499, demonstrating that at its highest investigational dose of 250 mg, the drug candidate elicited a strong reduction in viral load. VH499 was also safe and well-tolerated, with no side effects leading to treatment withdrawal.
GKS and ViiV reported that one patient, who was given a 25-mg dose of VH499, developed a genetic mutation “associated with reduced susceptibility to capsid inhibitors” on day 11, but stated in the announcement that the data, alongside encouraging Phase I results establishing VH499’s efficacy and tolerability, “support further development of VH499 as a potential long-acting antiretroviral for HIV treatment.”
GSK and ViiV also released data for another long-acting antiviral drug, VH184. All doses of the candidate elicited a “marked” reduction in HIV-1 viral load after 10 days of monotherapy. There were no resistance mutations detected.
