Merck (MRK) Reports New Data from Phase 2b Clinical Trial Evaluating Efficacy and Safety of Islatravir in Combination With Doravirine
Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced Week 144 data from the Phase 2b dose-ranging study evaluating the antiretroviral activity, tolerability, and safety of islatravir in combination with doravirine compared to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) in antiretroviral treatment-naïve adults with HIV-1. Phase 2b data through 144 weeks demonstrated that islatravir combined with doravirine continued to maintain viral suppression, as measured by the number of study participants achieving HIV-1 RNA levels <50 copies/mL, similar to DOR/3TC/TDF. The data further characterized the tolerability and safety profile of islatravir in combination with doravirine. The Week 144 results are a follow-up to the Week 96 results and safety data presented at the virtual 2020 International Congress on Drug Therapy in HIV Infection (HIV Glasgow 2020) and the virtual International AIDS Society Conference on HIV Science (IAS 2021), respectively. The Week 144 data were consistent with the Week 96 results in the 0.75 mg dose group (the selected Phase 3 dose), and were shared as an oral presentation during the 18th European AIDS Conference (EACS 2021) in London, U.K.
“We are encouraged by the Week 144 findings presented at EACS, which further support the potential of a two-drug doravirine/islatravir regimen for the treatment of HIV-1,” said Dr. Joan Butterton, vice president, global clinical development, infectious diseases, Merck Research Laboratories. “As we advance the ILLUMINATE clinical development program, we look forward to continuing to study this investigational treatment across diverse patient populations.”
Initial data from two pivotal ILLUMINATE Phase 3 clinical trials evaluating a combination product of doravirine/islatravir in virologically suppressed adults with HIV-1 switching from a stable antiretroviral regimen were also recently shared.
Islatravir is currently being evaluated 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. An overview of the islatravir treatment and prevention development program is available here.
Week 144 Efficacy and Safety Results from Phase 2b Study of Investigational Islatravir with Doravirine
In this international, multicenter clinical trial (NCT03272347), treatment-naïve adult participants with HIV-1 were randomly assigned (1:1:1:1) to one of four once-daily oral treatment groups: islatravir 0.25 mg (n=29), 0.75 mg (n=30), or 2.25 mg (n=31) in combination with doravirine (100 mg) and 3TC (300 mg) compared to DOR/3TC/TDF (n=31; Part 1). After a minimum of 24 weeks of treatment, participants in the islatravir treatment groups with HIV-1 RNA <50 copies/mL were transitioned to a two-drug regimen consisting of doravirine and islatravir, without 3TC (Part 2). Participants in the islatravir treatment groups then transitioned to 0.75 mg islatravir (the selected Phase 3 dose) plus doravirine between Weeks 60 to 84, and they continued the combination therapy through Week 144 (Part 3). At Week 144, participants switched to the fixed-dose combination of the selected dose of islatravir and doravirine as open-label treatment until the end of the trial at Week 192 (Part 4).
At Week 144, at all dose levels, islatravir combined with doravirine maintained virologic suppression as measured by the proportion of study participants achieving HIV-1 RNA levels <50 copies/mL: 72.4% (n=21/29), 83.3% (n=25/30), and 61.3% (n=19/31) of participants maintained virologic suppression in the 0.25 mg, 0.75 mg, and 2.25 mg islatravir combined with doravirine groups, respectively. Overall, 72.2% (n=65/90) of the combined islatravir with doravirine groups had HIV-RNA levels <50 copies/mL, which was similar to 77.4% (n=24/31) of the DOR/3TC/TDF group. Through Week 144, seven participants met the criteria for protocol-defined virologic failure (PDVF) (confirmed HIV-1 RNA ≥50 copies/mL) and discontinued treatment, all of whom had HIV-1 RNA levels <80 copies/mL. No participants met the criteria for clinically significant confirmed viremia (HIV-1 RNA ≥200 copies/mL) or viral drug resistance analysis.
The proportion of participants experiencing at least one adverse event (AE) at Week 144 was similar between the islatravir combined with doravirine and DOR/3TC/TDF groups. At Week 144, 89.7% (n=26/29), 90.0% (n=27/30), and 77.4% (n=24/31) of participants experienced AEs in the 0.25 mg, 0.75 mg, and 2.25 mg islatravir combined with doravirine groups, respectively. Additionally, 85.6% (n=77/90) of the combined islatravir combined with doravirine groups experienced AEs, as compared to 87.1% (n=27/31) in the DOR/3TC/TDF group. The most common drug-related AEs for the combined islatravir combined with doravirine groups versus DOR/3TC/TDF were diarrhea (1.1% [n=1/90] vs. 12.9% [n=4/31), nausea (3.3% [n=3/90] vs. 9.7% [n=3/31]), headache (2.2% [n=2/90] vs. 3.2% [n=1/31]), and abnormal dreams [2.2% [n=2/90] vs. 0% [n=0/31]). No additional islatravir combined with doravirine participants reported drug-related AEs after Week 48. The rate of discontinuations due to drug-related AEs was 2.2% (n=2/90) for the combined islatravir with doravirine groups and 3.2% (n=1/31) for DOR/3TC/TDF, all occurring before Week 48. There were no deaths or serious-drug-related AEs in the islatravir combined with doravirine groups.