Merck Initiates a Phase 3 Program for Islatravir

This week, Merck announced it was beginning a phase 3 program for its HIV therapy, islatravir. This will incorporate 3 trials studying the therapy with Pifeltro (doravirine).

All of the studies will evaluate a once-daily oral combination of doravirine 100 mg and a lower dose of islatravir (Dor/Isl). One study will evaluate the oral combination in previously untreated adults with HIV and two studies will evaluate Dor/Isl as a switch in antiretroviral therapy (ART) in adults with HIV- who are virologically suppressed. Study participants currently enrolled in once-daily treatment studies with doravirine 100 mg/ISL 0.75 mg will have the option of transitioning to a new study with the lower islatravir dose. The FDA has reviewed and agreed with this plan.

The investigational new drug application (IND) for the once-daily oral combination treatment program remains under a partial clinical hold for any studies that would use doses higher than the dose to be studied in this program.

In addition, the company is conducting a phase 2 study evaluating an investigational oral once-weekly combination of islatravir and Gilead’s lenacapavir in adults with HIV, and are virologically suppressed will resume under an amended protocol with a lower dose of islatravir. The IND under which the islatravir plus lenacapavir once-weekly treatment regimen is being investigated remains under a partial clinical hold for any studies that would use weekly oral islatravir doses higher than the doses considered for the revised clinical program.

Previously, the FDA had paused islatravir trials last December for PrEP usage as well as injectable islatravir for HIV and PrEP, and the oral doravirine/islatravir (Dor/Isl) for HIV.

The FDA’s reasoning for the pauses in Merck’s studies was a drop in T-cell counts in some participants receiving the therapy.

“We are grateful to the study investigators and the many participants in the trials of islatravir. 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,” Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a statement.

In its statement, Merck also announced it was discontinuing monthly oral islatravir development for PrEP. Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with a long intracellular half-life. The therapy works by converting to its active triphosphate (TP) form, islatravir-TP, within targeted cells. Islatravir-TP inhibits reverse transcriptase to suppress HIV replication. In addition to its long intracellular half-life, islatravir has high antiviral potency against HIV and its drug-resistant variants.

The company 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 in adults with HIV infection assessing MK-8527, a novel NRTTI candidate, will commence shortly. Merck will continue to engage with key stakeholders as it works to help address the unmet need in HIV prevention.

“We continue to believe in the potential of the NRTTI mechanism and we are evaluating additional candidates with the goal of helping to address unmet needs in HIV prevention,” Barr said in the same statement.