Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor
Authors' conclusion
This work validates the use of mRNA display technology for identification of novel oral therapeutic agents, exemplified by the identification of an oral PCSK9 inhibitor, which has the potential to be a highly effective cholesterol lowering therapy for patients in need.
Study context
- Population
- Healthy adults (single-dose trial); participants taking statins (multiple-dose trial)
- Outcome
- Free, unbound plasma PCSK9 (single oral doses, healthy adults) and LDL-C change from baseline (multiple oral doses, participants on statins)
Methodological detailsmRNA display screening, structure-based drug design, single rising-dose Phase 1 trial, multiple-dose Phase 1 trial
- mRNA display screening
- Structure-based drug design
- Single rising-dose Phase 1 trial
- Multiple-dose Phase 1 trial
Main finding
As reported in the abstract
Geometric mean reduction of free, unbound plasma PCSK9 with single oral doses of MK-0616 (healthy adults)
>93%
95% CI 84–103
Maximum geometric mean reduction in LDL-C from baseline after 14 days of once-daily 20 mg MK-0616 (participants on statins)
61%
95% CI 43–85
Original publication
Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor. Circulation. Published 1 May 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →