Merck known as MSD outside the United States and Canada, today announced an update regarding the Phase 2 IMAGINE-DR clinical trial (MK-8507-13), which is evaluating the investigational combination of MK-8507, a non-nucleoside reverse transcriptase inhibitor, and islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, as a once-weekly oral treatment for HIV-1 infection. MK-8507 and islatravir, alone and in combination, are investigational and not approved for use.
Decreases in total lymphocyte and CD4+ T-cell counts were observed in study participants randomized to receive ISL08507. A review by the external Data Monitoring Committee (eDMC) determined that this effect was related to treatment with the combination of ISL08507; the greatest decreases were seen in the arms of the study receiving the highest doses of MK-8507 (200 mg and 400 mg). At the recommendation of the eDMC, Merck is stopping dosing in the trial, with continued monitoring of study participants. The company has notified investigators and paused development of MK-8507. Merck remains confident in islatravir’s overall profile and is continuing with development of islatravir across a range of settings including in treatment of patients living with HIV and in pre-exposure prophylaxis (PrEP). None of these other programs combine islatravir with MK-8507.
“Merck remains resolute in its commitment to help address the unmet needs of people living with HIV and continue to do our part in the global efforts to help end the HIV pandemic, which includes the ongoing development of islatravir,” said Dr. Joan Butterton, vice president, infectious diseases, Global Clinical Development, Merck Research Laboratories. “All clinical studies provide important learnings to help us in the fight against HIV, and we are grateful to the patients and investigators for their contributions.”
In light of the findings from the MK-8507-013 study, Merck conducted a review of trends in total lymphocyte and CD4+ T-cell counts in company-sponsored clinical trials of ISL across all indications and dosing regimens. A dose-dependent decrease in lymphocyte counts was observed in an ongoing Phase 2 trial (MK-8591-016), which is evaluating monthly ISL (60 mg and 120 mg) for PrEP in participants at low-risk of HIV-1 infection. In this population of HIV-1 uninfected participants, the mean decreases were in the normal range and there was no increase in clinical adverse events (AEs) related to infection. In addition, a small, treatment related mean decrease in CD4+ T-cell counts was observed through Week 48 in two Phase 3 trials, ILLUMINATE SWITCH A and ILLUMINATE SWITCH B (MK-8591A-017 and MK-8591A-018), which are evaluating doravirine 100 mg in combination with ISL 0.75 mg daily (DOR/ISL) in HIV-1 virologically suppressed participants.
Merck has an expansive HIV clinical development program evaluating islatravir across a variety of dosing regimens, for both the treatment of HIV-1 in combination with other antiretroviral agents and for the prevention of HIV-1 as a monotherapy. Merck recently announced positive topline results from the ILLUMINATE SWITCH A and ILLUMINATE SWITCH B Phase 3 clinical trials. As previously reported, at 48 weeks, both trials met their primary efficacy endpoint of percentage of participants with HIV-1 RNA levels ≥50 copies/mL, demonstrating that antiviral efficacy was comparable between DOR/ISL and different antiretroviral therapy regimens (ILLUMINATE SWITCH A) and between DOR/ISL and bictegravir/emtricitabine/tenofovir (ILLUMINATE SWITCH B).
The IMAGINE-DR clinical trial was a Phase 2, randomized, controlled, double-blind, dose-ranging study, designed to evaluate a switch to MK-8507 and ISL in combination as a once-weekly oral treatment in adults with HIV-1 who have been virologically suppressed for greater than or equal to six months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. The study had been fully enrolled with 161 participants and was ongoing.
About PIFELTRO™ and DELSTRIGO™
PIFELTRO ™ (doravirine, 100 mg) is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.
DELSTRIGO™ (doravirine 100 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. DELSTRIGO contains a boxed warning regarding post-treatment acute exacerbations of hepatitis B (HBV) infection. See Selected Safety Information below.
About Islatravir (MK-8591)
Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation in more than 10 clinical trials. For treatment, islatravir is being evaluated in combination with other antiretrovirals, including the ILLUMINATE clinical trials program for a once-daily regimen. In the IMPOWER clinical trials, islatravir is also being studied for pre-exposure prophylaxis (PrEP) of HIV-1 infection as a single agent across a variety of formulations, including an oral once-monthly regimen.
For over 130 years, Merck, known as MSD outside the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world.
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