Merck Shares Additional Data From The Phase 3 Studies Of Two-drug Regimen Of Doravirine/Islatravir For HIV-1 Infection That Was Virologically Suppressed On Bictegravir/Emtricitabine/Tenofovir Alafenamidei In Trial MK-8591A-052 Or Antiretroviral Therapy In Trial MK-8591A-051

Author: Benzinga Newsdesk | October 15, 2025 05:48am

n trial MK-8591A-052, adults living with virally suppressed HIV-1 infection who switched to DOR/ISL from BIC/FTC/TAF showed minimal changes in weight and body composition at Week 48 (exploratory endpoints). These changes were comparable to trial participants who continued BIC/FTC/TAF.

In both trials, adults who switched to DOR/ISL from their current regimen (BIC/FTC/TAF or bART) saw no clinically meaningful changes in fasting lipids (exploratory endpoint in MK-8591A-052; secondary endpoint in MK-8591A-051) or in the homeostatic model assessment of insulin resistance (HOMA-IR) (exploratory endpoints). These changes were comparable to trial participants who continued on their respective prior antiretroviral therapy, BIC/FTC/TAF or bART. Participants who entered the trials on lipid-lowering therapy were excluded from the fasting lipids analysis. The percentage of participants who modified or initiated lipid-lowering therapy during the study was comparable across the treatment groups.

"Weight and body composition are often central concerns for people living with HIV, who may face obesity and other weight-related issues," said Dr. Chloe Orkin, dean for healthcare transformation, Queen Mary University of London. "The Week 48 results from the Phase 3 DOR/ISL trial (MK-8491A-052) are important to consider because they show minimal and similar changes in weight and body composition from baseline when participants switched to DOR/ISL."

"Comorbid conditions play an important role in the overall care for people living with HIV. Shifts in weight, body composition and lipids can increase the risk of cardiovascular disease and complicate management of other chronic illnesses," said Dr. Eliav Barr, senior vice president and chief medical officer, Merck Research Laboratories. "We are pleased that these data show that switching to DOR/ISL had minimal impact on weight and body composition and no clinically meaningful impact on fasting lipids in adults with virologically suppressed HIV-1 infection who switched from their current antiretroviral therapy."

In the double-blind trial MK-8591A-052, results for changes in weight and body composition showed that both the mean change and mean percent change in weight from baseline at Week 48 were minimal and similar in both treatment groups (exploratory endpoint): the mean weight change from baseline for the DOR/ISL treatment group was -0.03 kg (95% CI: -0.54, 0.48) vs. +0.28 kg (95% CI: -0.32, 0.88) for the BIC/FTC/TAF group, and the mean percentage weight change from baseline was 0.10% (95% CI: -0.50, 0.69) for DOR/ISL (n=316), compared to 0.39% (95% CI: -0.31, 1.09) for BIC/FTC/TAF (n=163). At Week 48, 14.6% and 3.5% of participants who switched to DOR/ISL experienced a ≥5% and ≥10% weight gain from baseline, respectively, compared with 16.0% and 2.5% of participants who continued BIC/FTC/TAF. Additionally, mean percent changes in lean body mass, peripheral fat and trunk fat and mean changes in body mass index and waist-to-hip ratio were small and comparable between the two treatment groups.

Across both trials (MK-8591A-052 and MK-8591A-051), the pooled DOR/ISL group's mean changes from baseline in fasting lipids, including total cholesterol, HDL, LDL and triglycerides were minimal, with no substantial differences from comparator groups (exploratory endpoint in MK-8591A-052; secondary endpoint in MK-8591A-051). Mean changes in fasting insulin, glucose and HOMA-IR were minimal across groups (exploratory endpoints). The proportion of participants with type 2 diabetes who modified their diabetic medication was <5% across treatment groups. A comparable proportion of participants initiated lipid-lowering therapy (pooled DOR/ISL 4.8%, BIC/FTC/TAF 4.1%, bART 5.9%) across the two trials.

Earlier this year, the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for DOR/ISL and has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA)

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