Benzinga | Dec 13, 2021 05:09PM EST

UPDATE: Merck Press Release Confirms Clinical Holds On Studies Evaluating Islatravir

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has placed clinical holds on the investigational new drug applications (INDs) for the oral and implant formulations of islatravir (MK-8591) for HIV-1 pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for HIV-1 treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) HIV-1 once-daily treatment. The FDA's clinical hold is based on previously announced observations of decreases in total lymphocyte and CD4+ T-cell counts in some participants receiving islatravir in clinical studies. As previously announced, Merck has stopped dosing in the Phase 2 IMAGINE-DR clinical trial of islatravir in combination with MK-8507 (MK-8591-013) and paused enrollment in the once-monthly Phase 3 PrEP studies, (MK-8591-022 and MK-8591-024) (see announcements here and here). With the FDA's clinical hold, no new studies may be initiated. Participants who are currently receiving islatravir as part of the studies for PrEP, including oral and implant formulations, as well as injectable islatravir for treatment and prophylaxis, will no longer receive the study drug; CD4+ T-cell and total lymphocyte counts will be monitored for recovery (full clinical hold). Participants in the PrEP studies will be offered approved, once-daily, oral PrEP. Additionally, participants in studies of DOR/ISL who were started on treatment will continue to receive study medication (partial clinical hold). No new participants will be screened or randomized in DOR/ISL studies for treatment during the partial clinical hold. Investigators have been informed of these actions.

"We are grateful to the participants and the study investigators for their ongoing contributions to this research," said Dr. Joan Butterton, vice president, infectious diseases, Global Clinical Development, Merck Research Laboratories. "Merck continues to investigate the potential of islatravir and nucleoside reverse transcriptase translocation inhibitors and remains committed to helping to address unmet needs in HIV treatment and prevention."

The following studies have been placed on full clinical hold:

* MK-8591-016 -- A Phase 2a PrEP study evaluating the safety and pharmacokinetics of oral islatravir once-monthly in participants at low risk of HIV-1 infection

* MK-8591-022 (IMPOWER 22) -- A Phase 3 PrEP study evaluating oral islatravir once-monthly in cisgender women at high risk for HIV-1 infection

* MK-8591-024 (IMPOWER 24) -- A Phase 3 PrEP study evaluating oral islatravir once-monthly in cisgender men and transgender women who have sex with men, and are at high risk for HIV-1 infection

* MK-8591-034 -- A Phase 1 study evaluating injectable islatravir (dosing complete)

* MK-8591-035 -- A Phase 2 PrEP study evaluating once-monthly oral islatravir in trans and gender diverse individuals (study had not yet opened enrollment)

* MK-8591-043 -- A Phase 2a PrEP study evaluating islatravir implant once-yearly in individuals at low risk for HIV-1 infection (study had not yet opened enrollment)

The following studies have been placed on partial clinical hold:

* MK-8591-011 -- A Phase 2 dose ranging study of oral DOR/ISL once-daily and lamivudine (3TC) in treatment-na?ve adult participants with HIV-1 infection (fully enrolled)

* MK-8591A-017 (ILLUMINATE SWITCH A) -- A Phase 3 oral once-daily, open label study evaluating a switch from antiretroviral therapy (ART) to DOR/ISL in adults with HIV-1 who are virologically suppressed (fully enrolled)

* MK-8591A-018 (ILLUMINATE SWITCH B) -- A Phase 3 oral once-daily study evaluating a switch from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) to DOR/ISL in adults with HIV-1 who are virologically suppressed (fully enrolled)

* MK-8591A-019 (ILLUMINATE HTE) -- A Phase 3 study evaluating oral islatravir and DOR/ISL once-daily in heavily treatment-experienced (HTE) participants with HIV-1 infection

* MK-8591A-020 (ILLUMINATE NAIVE) -- A Phase 3 study evaluating oral islatravir and DOR/ISL once-daily in treatment-na?ve participants with HIV-1 infection

* MK-8591A-028 (ILLUMINATE YOUTH) -- A Phase 2 open label study evaluating oral DOR/ISL once-daily for the treatment of HIV-1 infection in pediatric participants who are virologically suppressed on ART for ?3 months or are treatment-naive

* MK-8591A-033 -- A Phase 3 open label follow up of adult and pediatric participants with HIV-1 who were treated with oral DOR/ISL once-daily in earlier clinical studies

Additionally, Gilead and Merck have made the decision to stop all dosing of participants in the Phase 2 clinical study (NCT05052996) evaluating an oral-weekly combination treatment regimen of Merck's investigational islatravir and Gilead's investigational lenacapavir in people living with HIV who are virologically suppressed on antiretroviral therapy. This decision follows the joint announcement on November 23 of a temporary hold on further enrollment and screening in the study, which commenced in October 2021. Following this decision to stop dosing in the study, participants in both treatment groups will stop taking study drug and restart their prior antiretroviral regimen, as the two companies assess whether a different dosing of islatravir in combination with lenacapavir may provide a once-weekly oral therapy option for people living with HIV. Gilead and Merck remain committed to the collaboration, which aims to develop long-acting new treatment options to address the unmet needs for people living with HIV.