FDA further limit use of islatravir in ongoing studies
On 13 December 2021, Merck/MSD announced a further development concerning islatravir as an investigational compound for HIV treatment and prevention. 
This includes that the US FDA has now put clinical holds on the investigational new drug applications (INDs) for several compounds and indications,
- The oral and implant formulations of islatravir (MK-8591) for HIV-1 PrEP.
- The injectable formulation of islatravir for HIV-1 treatment and prophylaxis.
- The oral doravirine/islatravir (DOR/ISL) HIV-1 once-daily treatment.
This based on the concerns for mean reductions in total lymphocyte and CD4 counts reported in three earlier press statements. [2, 3]
This includes now stopping further dosing of the weekly oral formulation being studied with Gilead’s lenacapavir. [1, 4]
The following studies have been placed on full clinical hold. This includes stopping use of islatravir:
- 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)
- 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)
The following studies have been placed on partial clinical hold. This stops further enrolment but allows continued used of islatravir.
- MK-8591-011 – A phase 2 dose ranging study of oral DOR/ISL once-daily and lamivudine (3TC) in treatment-naïve 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-naïve 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 paediatric 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 paediatric participants with HIV-1 who were treated with oral DOR/ISL once-daily in earlier clinical studies
- Merck/MSD press release. Merck announces clinical holds on studies evaluation islatravir for the treatment and preventions of HIV-1 infection. (13 December 2021).
- Selected islatravir studies stop enrolment: further complications with important investigational drugs. HTB (6 December 2021).
- MSD/Merck stop once-weekly NNRTI MK-8507: islatravir studies continue with closer monitoring. HTB (November 2021).
- Gilead press statement. Gilead and Merck announce temporary pause in enrollment for phase 2 study evaluating an oral weekly combination regimen of investigational islatravir and investigational lenacapavir. (26 November 2021).
This report was first published on 16 December 2021.