Merck, known as MSD outside the United States and Canada, announced positive top-line results from two pivotal phase 3 trials of the investigational, once-daily oral fixed dose combination pill of doravirine/islatravir (DOR/ISL) in adults with HIV-1 infection who are virologically suppressed on different antiretroviral therapy regimens (ART; ILLUMINATE SWITCH A) or bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF; ILLUMINATE SWITCH B). 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 ART (ILLUMINATE SWITCH A) and between DOR/ISL and BIC/FTC/TAF (ILLUMINATE SWITCH B). The safety and tolerability profile of DOR/ISL during the trials to date are consistent with the previously reported phase 2 studies.
Doravirine is approved for the treatment of adults with HIV-1 in combination with other antiretrovirals, as a single agent (PIFELTRO) and a component of a single-tablet regimen (Delstrigo; DOR/3TC/TDF). Islatravir is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation for the treatment of people living with HIV-1 infection in combination with other antiretrovirals. Detailed findings from these studies will be presented at a future scientific congress and will form the basis of global regulatory applications.
“Merck is committed to investigating potential treatment options to help address the evolving needs of people living with HIV,” said Dr. Joan Butterton, vice president, global clinical development, infectious diseases, Merck Research Laboratories. “We are encouraged by the results from the phase 3 ILLUMINATE SWITCH A and B trials, in which the DOR/ISL dual regimen efficacy was comparable to certain commonly used three-drug regimens. We will continue to study doravirine/islatravir in diverse populations of people living with HIV and look forward to sharing data from these trials.”
The ILLUMINATE clinical trial program is evaluating DOR/ISL in a broad patient population, which includes people with HIV-1 who are virologically suppressed on ART, those who are heavily treatment experienced and those who are new to HIV treatment. The clinical trial program also includes pediatric participants with HIV-1 weighing at least 35 kg who are virologically suppressed and have not previously been treated. Merck is committed to enrolling diverse people in our HIV-1 clinical trials, especially among communities who may be disproportionately impacted by HIV, such as women and those within the Black and Latinx communities.
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.
The ILLUMINATE SWITCH A (MK-8591A-017) (NCT04223778) Study is a Phase 3, randomized, active-controlled, open-label clinical trial to evaluate a switch from antiretroviral therapy (ART) to investigational, oral, once-daily DOR/ISL (100 mg/0.75 mg) (MK-8591A), in adults with HIV-1 who are virologically suppressed. Participants (n=672) were randomized 1:1 to either switch to DOR/ISL or continue with their current baseline ART regimen through Week 48. At Week 48, all participants receive DOR/ISL through Week 96 of the trial. The primary efficacy (percentage of participants with HIV-1 RNA levels =50 copies/mL) and safety (number of participants experiencing adverse events (AEs) and discontinuing study intervention due to AEs) endpoints were assessed at Week 48.
The ILLUMINATE SWITCH B (MK-8591A-018) (NCT04223791) Study is a phase 3, randomized, double-blind clinical trial to evaluate a switch from BIC/FTC/TAF to investigational, oral, once-daily DOR/ISL (100 mg/0.75 mg), in adults with HIV-1 who are virologically suppressed. Participants (n=641) were randomized 1:1 to either switch to DOR/ISL or continue on BIC/FTC/TAF through Week 144. The primary efficacy (percentage of participants with HIV-1 RNA levels =50 copies/mL) and safety (number of participants experiencing AEs and discontinuing study intervention due to AEs) endpoints were assessed at Week 48.
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. An overview of the islatravir treatment and prevention development program is available here.
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