From its 17-year development cycle through to its commercial launch, production has always been in Yeztugo’s DNA. And, for the twice-yearly pre-exposure prophylaxis (PrEP) medication—which Gilead Sciences has positioned as a key tool to in the fight to end the HIV epidemic—“manufacturing is access.”
That’s according to Stacey Ma, Ph.D., Gilead’s executive vice president of pharmaceutical development and manufacturing. Those longstanding access considerations and the complex compound behind Yeztugo, lenacapavir, meant Gilead was baking process and scale-up considerations into its R&D efforts “from the beginning,” she told Fierce in a recent interview.
Yeztugo reached the end of its long road to approval last June, when the FDA blessed the injection as the first HIV prevention option that can be taken just twice a year. At the time, Gilead CEO Daniel O’Day heralded the drug as “one of the most important scientific breakthroughs of our time,” highlighting the “very real opportunity to help end the HIV epidemic” with Yeztugo.
The med has subsequently won clearance in the EU, too, and Gilead in parallel is pursuing approvals across continents and seeking accelerated reviews in certain low- or middle-income countries where it has opened additional access channels through royalty-free licensing deals with six generic drug makers.
Gilead in the interim has teamed up with the Global Fund to Fight AIDS, Tuberculosis and Malaria to commit enough Yeztugo doses to reach up to 2 million people over a three-year span, primarily in low- and lower-middle-income countries, while its generics partners work to come online—something Ma expects to occur around 2027. Gilead has pledged to provide those doses with the Global Fund at no profit.
Meanwhile, within its own network, Gilead is working on an lenacapavir-supporting expansion at the sterile product manufacturing facility in La Verne, California, that it opened in 2017.
Gilead got the ball rolling early on Yeztugo access, homing in on supply chain scale-up shortly after lenacapavir delivered impressive efficacy rates in HIV prevention trials in 2024, Ma said.
A key part of that process involved initiating tech transfers with Gilead’s six royalty-free partners—Dr. Reddy’s Laboratories, Emcure, Eva Pharma, Ferozsons Laboratories, Hetero and Viatris subsidiary Mylan—ahead of Yeztugo’s U.S. approval, Ma added. Widespread availability is necessary for the drug to have a meaningful impact on the HIV epidemic, she said.
Ma said she’s “extremely proud” of her team’s work to get the lenacapavir access piece in place early, noting that Gilead won U.S. approval for the drug in June and managed to deliver doses to two countries in sub-Saharan Africa last year within an “unprecedented” time frame of roughly six months.
And Gilead remains “very much on track” to deliver the remaining doses it’s pledged at no profit, she added.
Another impetus to ingrain production into Yeztugo’s development comes down to the complexity of lenacapavir itself, Ma suggested.
Speaking to that complexity, Ma described lenacapavir as a “large” small molecule and noted that there are about 50 chemical synthesis steps involved in making the API, which is roughly twice the amount needed for typical small molecules.
As an ultra-long-acting, twice-a-year injection, lenacapavir’s formulation is inherently unique—and comes with unique challenges, too—Ma pointed out. All told, the production process for the drug covers roughly 18 to 24 months, she said.
With the lessons learned through lenacapavir, Gilead plans to implement certain manufacturing insights into its broader HIV innovation efforts, plus those for other indications like oncology and inflammation, Ma pointed out.
One such lesson came in 2022, when the FDA placed a clinical hold on 10 lenacapavir studies over concerns about the compatibility of the drug solution with the material of the vials it was stored in. The FDA flagged the risk of the drug interacting with the borosilicate vials used at the time to produce “sub-visible” glass particles in the lenacapavir solution.
“Like any innovation, I think you will have little speed bumps here and there,” Ma said of the situation.
But Gilead forged on, and, despite receiving a complete response letter from the FDA tied to the compatibility issue, the company in May 2022 escaped its clinical hold after opting to pivot to alternative vials made of aluminosilicate glass.
“For this type of formulation, all the different pieces need to come together,” Ma explained.
Things are looking good so far for Yeztugo’s launch, which will reach its one-year anniversary in June.
Overall, the PrEP medication pulled down $150 million in the six months it was on the market last year, with $96 million in the fourth quarter alone, meeting Gilead’s sales guidance for 2025.
Speaking to analysts on a conference call in February, Gilead's chief commercial officer Johanna Mercier maintained that the drug is “well on its way” to blockbuster status, noting the company expects 2026 sales of Yeztugo to accelerate quickly to $800 million.