A Merck HIV drug put on clinical hold over safety concerns is now ready resume clinical trials in multiple studies, but at a lower dose and in a more limited range, the pharmaceutical giant said on Tuesday.
The The FDA stopped the tests of Merck’s antiviral drug, islatravir, after observing lower levels of two types of immune cells in patients treated with the drug. Of the five studies placed on full clinical hold late last year, two of them were phase 3 trials. An additional seven clinical trials were placed on partial hold, five of which were Phase 3 studies.
Rahway, New Jersey-based Merck said Tuesday that pivotal studies of islatravir will now test a lower dose of the once-daily pill. As in previous studies, these clinical trials will evaluate this drug in combination with Merck’s approved HIV drug doravirine, which is marketed as Pifeltro. One of the phase 3 studies will evaluate the combination in previously untreated adults who have HIV-1 infection. Two phase 3 trials will test the drug combination as a change in antiretroviral therapy in adults who have HIV-1 infection and are virologically suppressed. Merck said some clinical trial participants enrolled in a study evaluating once-daily doses of the drug combination will have the option to cross over to a new study with a lower dose of the test drug.
Islatravir is a type of medicine called a nucleoside reverse transcriptase translocation inhibitor (NRTTI), a new class of antiretroviral therapies. The small molecule is designed to use multiple mechanisms to suppress HIV. According to Merck, the FDA has reviewed and agreed to the new clinical trial plan for its experimental HIV drug. But an application seeking to start a clinical trial of a once-daily combination of islatravir and Pifeltro remains under a partial clinical hold for any studies that would use a dose higher than what will be studied under the new Phase 3 plan. Merck said , that a phase 1b study evaluating a different NRTTI drug candidate, MK-9527, will begin soon.
The new clinical trial plan also covers combining islatravir with Gilead Sciences’ antiviral drug, lencapavir. (The drug Gilead was recently approved in Europe where it is marketed under the name Sunlenca. The FDA’s decision is expected in December.) A Phase 2 clinical trial evaluating the combination of Merck and Gilead’s HIV drugs is now set to resume testing once-weekly dosing, with the Merck portion of the combination given at a lower dose.
Merck’s new HIV strategy abandons development of once-monthly dosing of islatravir for HIV pre-exposure prophylaxis (PrEP), or HIV prevention. Eliav Barr, senior vice president and head of global clinical development, chief medical officer of Merck Research Laboratories, said in a prepared statement that the company is continuing its partnership with the Bill & Melinda Gates Foundation focused on PrEP.
“We continue to believe in the potential of the NRTTI mechanism and are evaluating additional candidates to help address unmet needs in HIV prevention,” Barr said.
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