The long-running HIV market rivalry between Gilead Sciences and GSK is about to turn a new page this year as Gilead looks to disrupt the pre-exposure prophylaxis (PrEP) market with a twice-yearly injection.
The drug, called lenacapavir, has been billed to dominate—and expand—the HIV prevention field thanks to its more convenient dosing frequency and strong efficacy results from two phase 3 trials.
But GSK, with its bimonthly option Apretude, doesn’t think its rival can hog the entire long-acting market. The reason? Lenacapavir carries some unpleasant side effects, execs for London-based GSK explained to analysts on Wednesday.
For starters, there’s no doubt about the prevention power of lenacapavir, which is already approved in the U.S. under the brand name Sunlenca as part of a cocktail for heavily treatment-experienced patients with HIV.
In the phase 3 Purpose 1 trial, lenacapavir, used as a PrEP treatment, showed 100% efficacy against daily oral pills in women. In the phase 3 Purpose 2 trial, the capsid inhibitor delivered a 96% reduction in HIV infections compared with background HIV incidence or 89% compared with Gilead’s daily oral PrEP pill Truvada.
Lenacapavir’s convenience edge is also obvious. GSK itself is trying to develop a twice-yearly formulation, with a plan to start a registrational study around 2026.
Nevertheless, GSK’s president of corporate development, David Redfern, has flagged some tolerability concerns for lenacapavir, arguing that it “definitely won’t be for everyone.”
During a Wednesday call with investors, Redfern noted that 63% of individuals in lenacapavir’s Purpose 2 trial developed injection-site nodules—including seven cases of ulcer—lasting for a mean of about six months.
“For potential PrEP users who are body-image conscious, which will be quite a proportion of them, I think you know that potentially is an issue,” Redfern said.
In addition, lenacapavir has drug-drug interactions with several commonly prescribed drug classes, including corticosteroids and erectile dysfunction meds, he added. Some of these interactions can be serious.
“For potential PrEP users who are taking these meds, it may not be for them,” Redfern said. “We’ll see how this unfolds.”
In response to a Fierce Pharma request for comment, a Gilead spokesperson noted that across the two phase 3 trials that included more than 7,500 people, lenacapavir for PrEP was generally well-tolerated and had no significant or new safety concerns.
“Injection site reactions were relatively common and expected, and discontinuations were rare,” the Gilead spokesperson said. “This includes nodules, which were usually not visible and decreased notably with subsequent injections.”
As for drug-drug interactions, lenacapavir as PrEP can be co-administered with most commonly used medications, including contraceptives, gender-affirming hormones, common antidepressants, over-the-counter medications, and other medications used by the generally healthy individuals who would use PrEP, the Gilead spokesperson said.
Lenacapavir’s expected PrEP launch this summer is “one of the most awaited in the HIV market,” Citi analysts wrote in a January note. Gilead is positioning the drug to transform HIV prevention, which has been dogged by low adoption and poor adherence. The company hopes to grow the PrEP market from about 400,000 users in the U.S. to more than 1 million by 2033, when Gilead’s top-selling HIV treatment Biktarvy will lose market exclusivity.
Together with the updated oral drug Descovy, Citi analysts figure Gilead can achieve more than 60% share of the U.S. PrEP market by the mid-2030s, according to a December note to clients.
In their own December note, Leerink Partners analysts suggested Gilead’s goal is attainable because lenacapavir is “an exceptional product,” adding that “success is now about strategy and execution.” Still, execution won’t be easy because Gilead needs to grow the market beyond white men who have sex with men who are already managed by HIV providers, the Leerink analysts pointed out.
“Expanding this opportunity to additional consumers will require robust and successful direct-to-consumer (DTC) engagement, societal destigmatization of HIV (especially within certain populations), and new, changing care infrastructure for many providers,” the Leerink team said.