Selected islatravir studies stop enrolment: further complications with important investigational drugs
20 December 2021. Related: Antiretrovirals.
For the third time in just over two weeks, MSD/Merck have issued a press release reporting that investigational drug studies are have been stopped due to unexpected complications.
The latest press statement, issued on 6 December 2021, reported that the two large international phase 3 trials studying islatravir as a monthly oral tablet for PrEP were pausing further enrolment. [1]
Current participants in these studies – IMPOWER 22 (MK-8591-022) and IMPOWER 24 (MK-8591-024) – will continue to receive study drugs with additional monitoring. These randomised, double-blind, placebo-controlled studies compare monthly islatravir to either daily F/TAF or daily F/TDF.
The decision is based on a recommendation from an external data and monitoring committee.
Although the specific reason for the decision is not given, islatravir studies will include more frequent monitoring of total lymphocyte and CD4 cell counts.
Significant drops in both these immune markers led to a press statement on 18 November 2021 on stopping the development of the investigational NNRTI MK-8507. [2]
The limited details in that communication were based on a phase 2 study using MK-8507 and islatravir dual therapy. However, it also included references to islatravir monitoring.
On 23 November 2021, a joint press statement with Gilead Sciences announced that further enrolment into a phase 2 study of once-weekly oral lenacapavir plus islatravir for HIV treatment was also now on hold. [3]
comment
Given the potential for islatravir for both prevention and treatment this is another disappointment. It is important though that the studies are continuing, with additional monitoring to include CD4 monitoring. Recruitment will also hopefully resume, with modified entry criteria.
An earlier communication included that mean reductions in total lymphocytes of 21% and 36% were reported in the phase 2 islatravir PrEP study in the 60 mg and 120 mg arms monthly dose arms respectively (vs +4% increase in the placebo group). [2]
It is especially difficult that two different drugs from different classes both reported similar adverse event.
NOTE: On 13 December a further press release included details of additional studies that the FDA has put on hold – see next article in HTB. [4]
References
- MSD/Merck press statement. Merck announces pause in enrollment for two phase 3 clinical trials of investigational, once-monthly, oral islatravir for pre-exposure prophylaxis (PrEP) of HIV-1 infection enrolled participants will continue to receive study medicine. (6 December 2021).
https://www.merck.com/news/merck-announces-pause-in-enrollment-for-two-phase-3-clinical-trials-of-investigational-once-monthly-oral-islatravir-for-pre-exposure-prophylaxis-prep-of-hiv-1-infection
- 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 - MSD/Merck press statement. FDA further limits use of islatravir in ongoing studies. HTB (December 2021).
https://i-base.info/htb/41866
This report was first published on 6 December 2021.