From a 17-year development cycle to commercial launch, production has always been in Eztugo’s DNA. And for the twice-yearly pre-exposure prophylaxis (PrEP) drug that Gilead Sciences is positioning as a key tool in the fight to end the HIV epidemic, “manufacturing is access.”
said Dr. Stacey Marr, executive vice president of drug development and manufacturing at Gilead. These long-standing access considerations, and the complex compound behind Eztugo, lenacapavir, mean Gilead is building process and scale-up considerations into its research and development efforts “from the beginning,” she told Fierce in a recent interview.
Eztugo ended its long road to approval last June, with the FDA celebrating the shot as the first HIV prevention option that can be administered only twice a year. At the time, Gilead CEO Daniel O’Day touted the drug as “one of the most important scientific advances of our time” and highlighted the “very real opportunity” with Eztugo to help end the HIV epidemic.
The drug has since won approval in the EU, and Gilead is pursuing parallel continent-wide approval and expedited review in certain low- or middle-income countries, where it has opened additional access channels through royalty-free licensing agreements with six generic drug manufacturers.
Meanwhile, Gilead is working with the Global Fund to Fight AIDS, Tuberculosis and Malaria to bring enough Eztugo vaccine to reach up to 2 million people over three years, primarily in low- and middle-income countries, while its generic drug partners work to bring it online, which Ma expects to happen around 2027. Gilead has pledged to provide these vaccines to the Global Fund free of charge.
Meanwhile, within its network, Gilead is working to expand support for lenacapavir at its sterile product manufacturing facility in La Verne, Calif., which opened in 2017.
Gilead hit the ground early on accessing Eztugo, and made its home base to expand its supply chain shortly after lenacapavir achieved impressive efficacy rates in its 2024 HIV prevention trial, Ma said.
A key part of that process included initiating technology transfers with Gilead’s six royalty-free partners. Reddy’s Laboratories, Emcure, Eva Pharma, Ferroson’s Laboratories, Hetero, and Viatris subsidiary Mylan — ahead of Eztugo’s U.S. approval, Ma added. For the drug to have a meaningful impact on the HIV epidemic, it needs to be widely available, she said.
Ma said he was “very proud” of his team’s efforts to get lenacapavir up and running quickly, noting that Gilead won approval for the drug in the U.S. in June and successfully delivered the vaccine to two countries in sub-Saharan Africa in an “unprecedented” period of about six months last year.
And he added that Gilead is “very on track” to deliver the remaining doses promised without making a profit.
Another driver to incorporate production into Eztugo’s development is due to the complexity of the Lena Kapa building itself, Ma suggested.
Regarding its complexity, Ma described lenacapavir as a “big” small molecule, noting that manufacturing the API involves about 50 chemical synthesis steps, roughly twice the amount needed for a typical small molecule.
The formulation of lenacapavir, an ultra-long-acting twice-yearly injection, is unique in nature and comes with unique challenges, Ma noted. Overall, she said, the drug’s manufacturing process takes approximately 18 to 24 months.
Building on the lessons learned through lenacapavir, Gilead plans to bring certain manufacturing insights into its broader HIV innovation efforts, as well as other indications such as oncology and inflammation, Ma noted.
One such lesson is that in 2022, the FDA placed 10 studies of lenacapavir on clinical hold due to concerns about the compatibility of the drug solution with the material of the vial in which it was stored. The FDA warned that there was a risk that the drug could interact with the borosilicate vials used at the time, creating “invisible” glass particles in the lenacapavir solution.
“As with any innovation, I think there will be small slowdowns here and there,” Ma said of the situation.
However, Gilead moved forward and opted to convert to an alternative vial made of aluminosilicate glass, escaping the clinical hold in May 2022, despite receiving a full response letter from the FDA related to compatibility issues.
“This type of formulation requires all the different elements to come together,” Marr explained.
Eztugo’s launch is progressing smoothly so far, and it will celebrate its first anniversary in June.
Overall, PrEP drugs saved $150 million in the six months they were on the market last year, and $96 million in the fourth quarter alone, meeting Gilead’s 2025 sales guidance.
Gilead Chief Commercial Officer Johanna Mercier insisted to analysts on a February conference call that the drug is “on track” to become a blockbuster, noting that the company expects sales of Eztugo to rapidly accelerate to $800 million in 2026.
