Lipid-efficacy RCT · J Am Coll Cardiol 2023
MK-0616 phase 2b trial
Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.
The bottom line
In this phase 2b trial, the oral PCSK9 inhibitor MK-0616 produced large, dose-dependent LDL-C reductions compared with placebo and was well tolerated over 8 weeks of treatment plus 8 weeks of follow-up.
Primary lipid endpoint metUS status: US-approved 2026 (as enlicitide)
At a glance
- Medicine
- MK-0616 (enlicitide), oral PCSK9 inhibitor, 6, 12, 18, or 30 mg once daily
- Compared with
- Matching placebo
- People
- 381
- Who took part
- Adult participants with hypercholesterolemia and a wide range of atherosclerotic cardiovascular disease risk; 49% female, median age 62 years
- Design
- Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial
- Follow-up
- 8 weeks of treatment plus an additional 8 weeks of follow-up
- Main question
- Percentage change from baseline in LDL-C at Week 8; proportion of participants with adverse events (AEs) and study intervention discontinuations due to AEs
Main result
All doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage 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)
Effect on LDL cholesterol
Least squares mean percentage 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), P < 0.001 for all doses
Other results
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Safety
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.
In the trial's own words
“Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage 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.”
Quoted from the abstract of J Am Coll Cardiol 2023, checked word for word against PubMed. PubMed 36889610 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Enlicitide (Lipfendra)
Common questions
What did the MK-0616 phase 2b trial find?
In this phase 2b trial, the oral PCSK9 inhibitor MK-0616 produced large, dose-dependent LDL-C reductions compared with placebo and was well tolerated over 8 weeks of treatment plus 8 weeks of follow-up.
Who was in MK-0616 phase 2b?
381 people. Adult participants with hypercholesterolemia and a wide range of atherosclerotic cardiovascular disease risk; 49% female, median age 62 years.
What was MK-0616 phase 2b's main result?
All doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage 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)
How much did LDL cholesterol change in MK-0616 phase 2b?
Least squares mean percentage 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), P < 0.001 for all doses
Related trials
- LIBerate-HeFH (2023)In patients with heterozygous familial hypercholesterolaemia needing more LDL-C lowering, adding monthly subcutaneous lerodalcibep to therapy produced a large, highly significant LDL-C reduction versus placebo over 24 weeks with a safety profile similar to placebo aside from mild injection site reactions.
- ORION-3 (2023)Twice-yearly inclisiran produced durable, substantial LDL cholesterol and PCSK9 lowering over 4 years of repeated hepatic dosing and was well tolerated with low rates of serious drug-related adverse events.
- FOURIER-OLE (2022)Long-term evolocumab treatment after FOURIER maintained very low LDL-C with a persistently favorable safety profile over more than 8 years, and earlier initiation of evolocumab was associated with fewer cardiovascular events, including cardiovascular death, compared with delayed treatment start.
- HUYGENS (2022)Adding evolocumab to statin therapy after NSTEMI led to greater regression and stabilization of coronary plaque on imaging (thicker fibrous caps, smaller lipid cores, less plaque burden) compared with placebo.
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