FDA signs off on Gilead’s landmark long-acting PrEP med

 With the FDA’s much-anticipated nod for Gilead Sciences’ long-acting HIV pre-exposure prophylaxis (PrEP) injection Yeztugo (lenacapivir), a new era of HIV prevention has dawned.

The approval, which came a day ahead of its June 19 scheduled FDA decision date, marks the first for a twice-yearly PrEP option and fittingly comes just before the 13-year anniversary of the introduction of world’s first PrEP option, Gilead’s daily pill Truvada. 

Along with the convenience factor of the every-six-month injection, Yeztugo also touts competitive efficacy proven through two large phase 3 studies. Gilead has touted its clinical effort as the “most comprehensive and diverse HIV prevention trial program ever conducted."

In Gilead’s PURPOSE 1 trial of cisgender women at sites across South Africa and Uganda, Yeztugo use yielded an unprecedented 100% efficacy rate, with zero HIV infections observed across the treatment group. The drug also demonstrated its superiority when compared to Gilead's own Truvada, the results showed.

The PURPOSE 2 trial, meanwhile, tested the long-acting PrEP drug in a broader population that included cisgender gay and bisexual men, transgender people and non-binary people at sites across the world. Again, Yeztugo proved to be widely effective at reducing HIV infections; 99.9% of those who took the twice-yearly option did not acquire HIV, with only two cases reported out of more than 2,000 participants. The result showed that Yeztugo is 89% more effective at reducing HIV than once-daily Truvada, the company pointed out.

In studying Yeztugo across the PURPOSE trials, Gilead noted adherence issues with the once-daily comparators Truvada and its newer option, Descovy. With two yearly injections of Yeztugo, PrEP users can “get it and forget it” instead of having to remember to take a daily pill, Jared Baeten, M.D., Ph.D., Gilead’s SVP of clinical development and head of virology, explained in a recent interview with Fierce Pharma.

It's all a part of the company’s plan to “redefine the PrEP market” as a whole, chief commercial officer Johanna Mercier noted on an earnings call last summer. While Gilead already has a hold on the PrEP market with its existing pills, “new options” are needed to work toward the goal of “ending infections in this country and around the world,” Baeten said.

Now, with the FDA’s blessing, the company can hit the ground running with the “thoughtful and creative” rollout it’s been plotting (PDF) for months now.

Gilead has already set up agreements with six drugmakers that were given a royalty-free license to make and supply low-cost versions of the long-acting PrEP option in 120 high-incidence, resource limited countries. It also is utilizing the European Medicines Agency’s EU-Medicines for all program to allow other drug regulators to leverage Europe’s accelerated review of the drug for their own assessments, potentially speeding up broader global access.

“We see the potential for lenacapivir to be a medicine of global impact,” Baeton said. “We’re pushing on all sides to make sure that the impact at the global scale is going to fulfill the promise that lenacapivir holds.”

Even so, to deliver on its goal of widening the existing PrEP market, “targeted approaches” will be needed to unlock underpenetrated markets overseas, Citi analysts pointed out in a December note to clients. In the U.S., Gilead looks to expand the 400,000-person PrEP market to more than 1 million people by the mid-2030s.

Yeztugo marks another feather in Gilead's cap when it comes to the company's leading HIV portfolio. The drug's active ingredient, lenacapivir, was first approved several years ago for adults with multi-drug-resistant HIV under the brand name Sunlenca. It’s a “tiny, tiny population,” Baeton said, but one that the company is “so proud” to treat.

Despite the company’s work in other treatment areas like oncology and liver disease, Gilead's HIV products continue to make up the majority of its overall sales, driven largely by HIV treatment Biktarvy. 

Gilead hasn’t yet offered specific sales expectations for Yeztugo, but it expects the current PrEP market to grow “quite rapidly” upon launch considering that many PrEP-naïve people are “hanging in there” until it’s available, Mercier said on an April earnings call. Mizuho analysts previously put lenacapavir's peak annual sales potential at around $4 billion.

Until now, GSK’s 2021-approved every-two-month Apretude was the longest-acting player in the PrEP market. Considering that lenacapivir’s launch is “one of the most awaited in the HIV market,” Citi analysts figure Gilead’s PrEP portfolio can secure more than 60% share of the U.S. PrEP market by the mid-2030s, according to a December note to clients. 

https://www.fiercepharma.com/pharma/its-here-fda-signs-gileads-landmark-long-acting-prep-signaling-new-era-hiv-prevention