Merck Halts Clinical Development of Non-Nucleoside Reverse Transcriptase Inhibitor MK-8507 Due to Declines in White Blood Cell Counts
Nov 20, 2021 23:57
CST Updated
23:57
MSD
Pharmaceutical R&D and Manufacturer
News on November 20, 2021 /BioValleyBIOON/ -- MSD (Merck & Co) recently announced an update on the Phase 2 IMAGINE-DR clinical study (MK-8507-13). The trial is evaluating the experimental combination of MK-8507 and islatravir (ISL) as a once-weekly oral regimen for the treatment of HIV-1 infection.MK-8507 is a non-nucleoside reverse transcriptase inhibitor (NNRTI), and islatravir is a novel oral nucleoside reverse transcriptase translocation inhibitor (NRTTI).
In the aforementioned study, patients randomly assigned to receive ISL+MK-8507 treatmentA decrease in the total lymphocyte count and CD4+ T cell count was observed.. The External Data Monitoring Committee (eDMC) reviewed and determined,This effect is associated with the combination therapy of ISL and MK-8507. The greatest decrease was observed in the study groups receiving the highest doses of MK-8507 (200mg and 400mg).
Based on the recommendation of the eDMC, MSD is discontinuing dosing in patients participating in the trial and will continue to monitor the patients. MSD has informed the investigators and paused the development of MK-8507. MSD remains confident in the overall profile of islatravir and continues to develop islatravir across a range of settings, including treatment for people living with HIV-1 and for pre-exposure prophylaxis (PrEP). None of these other programs involve the combination of islatravir with MK-8507.
Based on the results of the MK-8507-013 study, Merck Sharp & Dohme AG has implemented ISL sponsored by the company across all indications and dosing regimens.Clinical TrialThe trends in total lymphocyte and CD4+ T cell counts were reviewed.
Islatravir (MK-8591) Chemical Structure (Image Source: medchemexpress.cn)
A dose-dependent decrease in lymphocyte count was observed in the ongoing Phase 2 trial (MK-8591-016), which evaluates once-monthly ISL (60mg and 120mg) for PrEP in subjects with low risk of HIV-1 infection. In these subjects not infected with HIV-1, the average decrease was within the normal range, with no increase in infection-related clinical adverse events (AE).
In addition, in two Phase 3 trials, ILLUMINATE SWITCH A (MK-8591A-017) and ILLUMINATE SWITCH B (MK-8591A-018)A slight, treatment-related decrease in CD4+ T-cell count was observed during treatment up to Cycle 48.. These two trials are evaluating the DOR/ISL combination (DOR/ISL, 100mg/0.75mg, once daily) in HIV-1 infected individuals who have achieved virologic suppression. Compared to the control group, patients receiving DOR/ISL treatment did not show an increased incidence of infection-related adverse events over 48 weeks. MSD has informed the investigators of these trials that they will continue. Full results will be presented at an upcoming medicalConferencePublished on.
MSD has an extensive HIV clinical development program evaluating various dosing regimens of islatravir, including: combination therapy with other antiretroviral drugs for the treatment of HIV-1, and as monotherapy for the prevention of HIV-1. Recently, MSD announced positive results from two Phase 3 trials, ILLUMINATE SWITCH A (MK-8591A-017) and ILLUMINATE SWITCH B (MK-8591A-018). As previously stated, at 48 weeks, both trials met their primary efficacy endpoints (the proportion of patients with HIV-1 RNA levels ≥50 copies/mL), demonstrating that DOR/ISL and different antiretroviral treatment regimens (ILLUMINATE SWITCH A study), as well as DOR/ISL compared to Gilead's triple-combination drug Biktarvy (BIC/FTC/TAF) (ILLUMINATE SWITCH B study), showed similar antiviral efficacy. (Bioon.com)