Merck’s Phase 2 HIV Treatment Study Resumes with Phase 3 Program Announcement

On September 20, Merck announced the initiation of a Phase 3 clinical program studying once-daily islatravir an HIV-1 treatment. This announcement comes as the Phase 2 trial evaluating islatravir resumes with amended conditions. The new studies will evaluate islatravir in combination with doravirine.

Related Article: A Cure for HIV Could Be Here Sooner Than You Think – Future of Health

How Does Islatravir Work?

Islatravir is an investigational treatment belonging to a group of HIV drugs known as nucleoside reverse transcriptase translocation inhibitors (NRTTIs). NRTIs inhibit an HIV enzyme called reverse transcriptase, which the virus uses to convert its RNA to DNA. When NRTIs prevent this function, HIV cannot replicate.

Another example of an NRTTI is VIDEX (didanosine). Approved by the United States Food and Drug Administration (FDA) in 2000, it treats HIV-1 infections in combination with other drugs, similar to islatravir.

Several Phase 2 Studies were evaluating islatravir in 2021. Notable among them is NCT05052996. The purpose of this study was the evaluation of the efficacy of islatravir in combination with the investigational capsid inhibitor lenacapavir. However, on December 13, 2021, the FDA placed holds on all islatravir clinical trials. The basis of this hold was the observation of decreases in total lymphocyte and CD4+ T-cell counts in some participants of the studies. 

With Merck’s Phase 3 program announcement, the Phase 2 trial resumes, albeit with a lower dose of islatravir.

What will the Phase 3 Program Evaluate?

The plan for Merck’s new Phase 3 studies is the evaluation of a once-daily lower dose of islatravir in combination with doravirine 100 mg (DOR/ISL). One study of the program plans to evaluate DOR/ISL in previously untreated adults with HIV-1 infection. Meanwhile, two other studies will evaluate DOR/ISL as a switch in antiretroviral therapy (ART) in virologically suppressed adults with HIV-1 infection. 

The Phase 2 NCT05052996 trial will resume, similarly with a lower dose of islatravir. However, Merck also announced the discontinuation of the ongoing Phase 3 PrEP once-monthly oral islatravir trial. Merck will continue to monitor participants from the study.

On the new program Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer at Merck Research Laboratories, said, “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.”

With the FDA reviewing and agreeing with Merck’s plan, the new clinical trials will begin in the near future. As for NCT05052996, Merck expects its primary completion in August 2023, with its total completion following in December 2027.

Author

Max Heirich