Gilead Sciences is no stranger to making history in HIV. Twelve years after the drugmaker pushed the first pre-exposure prophylaxis (PrEP) HIV med, Truvada, over the FDA finish line, new results from a second pivotal study of its long-acting drug could soon yield another market-changing approval.

In a study of more than 3,000 cisgender men, transgender men, transgender women and gender non-binary individuals ages 16 and older, only two out of the 2,180 who took Gilead’s twice-yearly lenacapavir as a PrEP med acquired HIV, the company said Thursday. The study enrolled participants who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the U.S.

Lenacapavir delivered a a 96% reduction in HIV infections compared with background HIV incidence (bHIV), Gilead said.

The PURPOSE 2 study met its key endpoints of superiority over bHIV and once-daily Truvada at an interim analysis, the independent data monitoring committee confirmed. Investigators are wrapping up the blinded phase of the study and are now offering open-label lenacapavir to all patients.

Nine participants in the Truvada group were infected, making lenacapavir 89% more effective than Gilead’s flagship PrEP med.

Last year’s PURPOSE 1 trial in cisgender women and adolescent girls in South Africa and Uganda was also unblinded early after meeting an unprecedented 100% efficacy bar, with 0 infections over the trial period for those taking lenacapavir. That study alone led Mizuho analyst Salim Syed to believe that the drug is “probably well situated” to take a significant share of the PrEP market, he wrote in a note at the time.

“With such remarkable outcomes across two Phase 3 studies, lenacapavir has demonstrated the potential to transform the prevention of HIV and help to end the epidemic,” CEO Daniel O’Day said in the company’s press release. “Now that we have a comprehensive dataset across multiple study populations, Gilead will work urgently with regulatory, government, public health and community partners to ensure that, if approved, we can deliver twice-yearly lenacapavir for PrEP worldwide, for all those who want or need PrEP.”

Gilead will kick off global regulatory filings by the end of this year in an effort to deliver on a 2025 launch. Meanwhile, Gilead is also working to finalize contracts such as voluntary licensing partnerships that would support lenacapavir access in countries “where the need is greatest,” the company said. That's part of a wider access strategy that prioritizes speedy approvals in high-incidence and low-resource regions of the world, according to Gilead.

Lenacapavir first hit the market in 2022 under the brand name Sunlenca for use alongside other agents in patients with multidrug-resistant HIV. That patient population makes up 2% of adults living with HIV. 

With the new opportunity to market the drug as a long-acting PrEP, the company is looking to make waves and “redefine the PrEP market as a whole,” chief commercial officer Johanna Mercier said last month on Gilead’s second-quarter earnings call. 

“Because adherence to oral products can be challenging for some people, twice-yearly injectable lenacapavir for PrEP has the potential to be one of the most impactful interventions we could have to drive down new infections and bring us closer to ending the HIV epidemic in the United States,” PURPOSE 2 principal investigator and professor of medicine at Emory University, Colleen Kelly, M.D., explained in a statement.

Mizuho's team has put lenacapavir's peak sales at around $4 billion, according to a Thursday note to clients. 

GSK is also a player in the long-acting PrEP market, having launched its every-two-month offering Apretude in 2021. GSK plans launches for every-four-month and every-six-month options later this decade.