FDA further limit use of islatravir in ongoing studies
20 December 2021. Related: Antiretrovirals.
Simon Collins
On 13 December 2021, Merck/MSD announced a further development concerning islatravir as an investigational compound for HIV treatment and prevention. [1]
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
References
- Merck/MSD press release. Merck announces clinical holds on studies evaluation islatravir for the treatment and preventions of HIV-1 infection. (13 December 2021).
https://www.merck.com/news/merck-announces-clinical-holds-on-studies-evaluating-islatravir-for-the-treatment-and-prevention-of-hiv-1-infection - Selected islatravir studies stop enrolment: further complications with important investigational drugs. HTB (6 December 2021).
https://i-base.info/htb/41833 - MSD/Merck stop once-weekly NNRTI MK-8507: islatravir studies continue with closer monitoring. HTB (November 2021).
https://i-base.info/htb/41647 - 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).
https://www.gilead.com/news-and-press/company-statements/gilead-and-merck-announce-temporary-pause-in-enrollment-for-phase-2-study-evaluating-an-oral-weekly-combination-regimen-of-investigational-islatravir-and-investigational-lenacapavir
This report was first published on 16 December 2021.