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A worrisome safety signal slows Merck’s HIV ambitions

Currently, the world’s best-selling HIV medications are made up of at least three “active ingredients.” But recent years have seen increasing interest in treatments that contain fewer drugs, which, in theory, would make them more tolerable to patients. Companies like GlaxoSmithKline and Johnson & Johnson have specifically set their sights on regimens comprised of two drugs. Merck favors this approach as well, and has touted the potential of islatravir to be a “foundational anchor” for two-drug treatments.

Just last month, the company announced positive results from a pair of large clinical trials that tested islatravir plus doravirine, the active ingredient in Merck’s approved HIV medicine Pifeltro. After following participants for almost a year, study investigators found Merck’s combination kept HIV infections in check as well as other antiretroviral therapy regimens, with one trial showing it was comparable to Gilead’s Biktarvy, a three-drug combination that holds a significant portion of the HIV drug market.

Islatravir is also at the center of a deal inked early this year, which revolves around testing it in combination with an experimental Gilead drug called lenacapavir.

Yet, a safety signal like the one disclosed Thursday could create a problem for Merck.

While development will continue, it doesn’t look as though islatravir is entirely in the clear. Merck said that, in light of the recent findings, it reviewed the white blood cell counts in company-sponsored clinical trials of islatravir across all indications and dosing regimens. The company found a “dose-dependent decrease in lymphocyte counts” in an ongoing mid-stage study evaluating monthly doses of the drug as pre-exposure prophylaxis, or PrEP, in people at low-risk of HIV infection.

Merck noted that these decreases were, on average, still in the normal range, and there was no increase in clinical adverse events related to infection.

The company also discovered in those two large, positive clinical trials a small decrease in a type of T-cell among patients who received the islatravir combination therapy. Yet there, too, Merck found no increased incidence of infection-related adverse events relative to comparators.

Though Merck says it remains confident in its drug, the updates could weigh on islatravir programs, according to Brian Abrahams of RBC Capital Markets. In a note to clients, the analyst wrote that his team believes “the newly arising safety uncertainties could substantially reduce the potential for meaningful switches off” of Gilead’s drugs and onto Merck’s islatravir-containing regimens.

That presents a double-edge sword for Gilead. On the one hand, islatravir is a potential competitor to the company’s market-leading portfolio of HIV medications. On the other, these new safety concerns may push Gilead to look elsewhere for a drug to combine with lenacapavir.

Merck’s share price was down close to 3% in late Friday morning trading, while Gilead’s remained relatively unchanged.