Merck finally gets FDA nod to relaunch HIV trials, but drops preventive therapy plans

A path forward for Merck & Co.’s struggling HIV strategy has opened up, with the FDA releasing a nine-month clinical hold on trials of the Big Pharma’s drug islatravir as long as low doses are used. However, the company has also decided to ditch its plans to explore the drug as a preventive treatment.

The agency slapped the hold on trials of islatravir to both treat and prevent HIV in December 2021, citing decreases in total lymphocyte and CD4+ T-cell counts in some patients receiving the therapy. The previous month, Merck had pumped the brakes on trials of another potential HIV asset, dubbed MK-8507, over similar concerns.

Now, the FDA has given the green light to three new phase 3 trials of a 0.75-mg dose of islatravir in combination with Merck’s approved HIV drug Pifeltro. One study will evaluate the drugs in previously untreated adults with HIV-1 infection, while two more trials will evaluate it as a switch in antiretroviral therapy in adults with HIV-1 infection who are virologically suppressed. Studies of higher doses of islatravir remain on ice.

Swapping in a lower dose of islatravir also means a separate phase 2 trial can now continue, namely a weekly combination regimen of the drug and Gilead Sciences' lenacapavir in adults with HIV-1 infection who are virologically suppressed, Merck added.

But it’s not all good news for the reinvigorated islatravir pathway. Merck will discontinue its development of the drug for preexposure prophylaxis (PrEP) after “careful evaluation and analysis.” Participants in the ongoing phase 3 PrEP once-monthly oral studies will still be monitored, said the company, which added that it would continue its partnership with the Bill & Melinda Gates Foundation to evaluate potential long-acting PrEP opportunities.

Merck also “remains committed to developing compounds for long-acting HIV prevention and believes in the potential of the nucleoside reverse transcriptase translocation inhibitor (NRTTI) mechanism.” A phase 1b study of MK-8527, a novel NRTTI candidate, is due to begin “shortly,” the company said.