The Food and Drug Administration has allowed Merck & Co. to move forward with testing of its experimental HIV drug islatravir at a lower dose, nearly a year after safety concerns derailed a dozen of the company’s studies.
Under an agreement with the agency announced Tuesday, Merck will begin three new Phase 3 clinical trials of islatravir in combination with its approved HIV medicine Pifeltro — two in previously untreated adults with HIV-1 infection and a third in adults who are virologically suppressed on other antiviral drugs. These new trials will use a lower dose of islatravir than previously studied.
Additionally, Merck and research partner Gilead Sciences will restart a Phase 2 study of islatravir and the latter company’s HIV drug lenacapavir, but using a reduced dose of Merck’s medicine.
A partial clinical hold, put in place by the FDA last year, remains in place for any studies using higher doses than those planned for under the new agreement with the regulator.
“Following extensive evaluations and consultation with FDA, we are pleased to be able to initiate our new Phase 3 clinical program to evaluate islatravir for the treatment of HIV-1 infection,” said Eliav Barr, chief medical officer at Merck Research Laboratories, in the Tuesday statement.
However, Merck will discontinue development of its once-monthly oral formulation of islatravir for use in pre-exposure prophylaxis, or PrEP. The company said it “remains committed” to developing new medicines for long-acting HIV protection and will soon start a Phase 1 trial of another compound that works in a similar fashion as islatravir.
Islatravir is one of Merck’s most important experimental medicines, a drug it has pitched as “the foundation of future Merck HIV treatment and prevention regimens.” It’s meant to be well suited for use in two-drug HIV treatment combinations, including regimens designed for less frequent administration. The company has been developing it in oral, injectable and even an implant formulation.
But late last fall, Merck was forced to halt dosing in a study of the drug after researchers reported that some patients had experienced drops in certain kinds of white blood cells. A week later, Merck and Gilead paused enrollment in a trial testing islatravir and lenacapavir together.
The FDA followed in December with a clinical hold on six studies of islatravir for PrEP and treatment, as well as a partial hold on seven more testing it in combination.