Gilead underscored its faith in the combo therapy and pledged to work with regulators to resolve the hold, which has paused five clinical trials. Gilead also stressed that the hold does not impact any other assets in its HIV pipeline.
Five clinical trials for Gilead’s investigational weekly HIV combo pill have been placed on hold by the FDA after a safety signal emerged. While the combo includes a version of Gilead’s lenacapavir, which is approved as Sunleca for twice-yearly treatment of people with multi-drug-resistant HIV and currently under FDA review for the prevention of HIV, Jefferies analysts said the pause will not affect the looming decision date.
Gilead announced the clinical hold Tuesday morning, explaining in a release that two Phase II/III trials named WONDERS-1 and -2 had been paused, plus three Phase I studies. The combination therapy features the integrase strand transfer inhibitor GS-1720 and/or the capsid inhibitor GS-4182. While Gilead did not mention lenacapavir in the release, Jefferies analysts explained that GS-4182 is a pro-drug formulation of the investigational therapy, which is separately under review for HIV pre-exposure prophylaxis (PrEP).
“While it might increase some investor uncertainty into the all-important June 19 PDUFA for [lenacapavir] for PrEP, we see no major read-through and expect an on-time and clean FDA approval,” Jefferies wrote on Tuesday morning.
BMO Capital Markets agreed but said that Gilead’s shares could still face some pressure Tuesday as investors digest the news. The company’s stock declined 2% to $110.75 as of 10:50 a.m. ET.
Gilead said that the hold was placed after decreases in CD4+ T cell and absolute lymphocyte counts were identified in a subset of patients who received both drugs. This can be a signal of a weakened immune system in patients with HIV.
The Phase II/III WONDERS-1 trial is comparing the combo with Gilead’s approved HIV medicine Biktarvy in people with HIV who are taking medication to suppress the virus. The Phase II/III WONDERS-2 study similarly features Biktarvy as the comparator but has enrolled patients with HIV who are treatment-naive.
The company underscored its faith in the combo therapy and pledged to work with regulators to resolve the hold. Gilead also stressed that the hold does not impact any other assets in its HIV pipeline.
Jefferies agreed with this assessment, noting that had the FDA been concerned, it would have stalled more of Gilead’s formulations and integrase inhibitors currently under development.
Any Day Now
Gilead is seeking approval of lenacapavir as a twice-yearly injection for PrEP for HIV. The FDA’s decision, due June 19, has been eagerly anticipated by analysts, patients and Gilead, which is gearing up for a massive launch. The company is looking to the drug to build on its HIV empire, which is anchored by Biktarvy—a drug that recorded sales of $13.4 billion in 2024. BMO predicts peak sales of $6.5 billion for the PrEP indication. More broadly, Gilead is aiming to launch nine new HIV drugs by 2033.
Gilead backed lenacapavir’s latest application with data from the Phase III PURPOSE 1 and PURPOSE 2 studies. PURPOSE 1, which focused on cisgender women, demonstrated 100% efficacy in preventing HIV infection. PURPOSE 2 enrolled a more diverse population of cisgender men, transgender men, transgender women and nonbinary individuals who have sex with partners assigned male at birth. Results showed that twice-yearly lenacapavir cut HIV incidence by 96%.
Jefferies said this indication is very different from what the combo has been aimed at addressing in the now-stalled trials. It’s also unclear if the lenacapavir pro-drug is even the issue at this point.
Other companies in the HIV space have had similar safety signals arise. Merck, for example, had trials of Isentress, launched in 2007, placed on hold by the FDA after CD4 T cell count reductions were observed. A combo of Isentress and Gilead’s lenacapavir for HIV treatment was also placed on hold several years ago but was ultimately released in 2022 using lower doses of Merck’s drug.
Altogether, Jefferies is not too worried about the clinical hold. The firm places more weight on Phase I data for lenacapavir in combination with the injectable integrase inhibitors GS-1219 and GS-3242. Gilead intends to pick one of those medicines to move forward in a combo regimen with lenacapavir by the end of the year. The drugs are administered as a single dose at the first month and sixth month (Q6M).
“This would be the real game changer and value proposition for Gilead if they are able to swap the $15B Biktarvy market onto long-acting Q6M injectable in the later half of the decade,” Jefferies wrote.
