Efficacy and safety of the oral PCSK9 inhibitor MK-0616: a phase 2b randomized controlled trial
Abstract
BACKGROUND
MK-0616 is an oral PCSK9 macrocyclic peptide inhibitor in development for the treatment of hypercholesterolemia.
OBJECTIVES
This Phase 2b, randomized, double-blind, placebo-controlled, multi-center trial (NCT05261126) aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia.
METHODS
This study planned to include 375 adult participants with a wide range of ASCVD risk. Participants were assigned randomly (1:1:1:1:1 ratio) to MK-0616 (6, 12, 18, or 30 mg QD) or matching placebo. The primary endpoints included percent change from baseline in LDL-C at Week 8 and the proportion of participants with adverse events (AE) and study intervention discontinuations due to AEs; participants were monitored for AEs for an additional 8 weeks after the treatment period.
RESULTS
Of the 381 participants randomized, 49% were female, and median age was 62 years. Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (p<0.001) differences in LS mean % change in LDL-C from baseline to Week 8 vs. placebo: -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5% to 43.4%) as placebo (44.0%). Discontinuations due to AEs occurred in 2 or fewer participants in any treatment group.
CONCLUSIONS
MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 616 participants or records.
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