MK-0616, an oral PCSK9 inhibitor, met its primary endpoint in a Phase 2 study, significantly reducing LDL cholesterol levels in patients with hypercholesterolemia at doses of 6 mg to 30 mg compared to placebo. ApoB and non-HDL cholesterol levels have also been reduced.
«These data support the further development of MK-0616, which may improve access to effective LDL-cholesterol-lowering therapies and thus the achievement of the LDL cholesterol targets recommended in guidelines and thus reduce cardiovascular risk,» concludes Prof.Dr. Christie M. Ballantyne, Center for Metabolic Disease Prevention, Baylor College of Medicine in Houston, from the results of a Phase 2b study he presented at the Annual Scientific Meeting of the American College of Cardiology () in conjunction with the World Congress of Cardiology (WCC) in New Orleans [1].
«This is a pleasing study,» commented Prof. Dr. Rhonda M. Cooper-DeHoff, University of Florida at Gainesville. So far, there have been access problems with PCSK9 inhibitors due to parenteral administration and high costs. However, it is still unclear when this oral substance will be commercially available.
LDL cholesterol target value often not reached
It has long been known that elevated LDL cholesterol levels are a cause of atherosclerotic diseases. Although effective therapies are available with statins, for example, a number of patients achieve the target values defined in guidelines.Injectable PCSK9 inhibitors have been shown to be highly effective in reducing LDL cholesterol levels and lowering the risk of atherosclerotic events. However, high costs and parenteral administration make access difficult. The PSCK9 inhibitors evolocumab and alirocumab available to date are monoclonal antibodies. Inclisiran is an siRNA, but all must be administered parenterally.
Orally administered MK-0616
The oral MK-0616 is the result of a collaboration between MSD Merck Sharp & Dohme and the US company RA-Pharmaceuticals, which is involved in the production of macrocyclic peptides. The macrocyclic peptide binds to PSCK9 and inhibits its interaction with LDL receptors.
The Phase 2b randomized, double-blind, multicenter study presented by Ballantyne evaluated the efficacy and safety of daily MK-0616 compared to placebo. Participants aged 18 to 80 years with hypercholesterolemia and a moderate to high risk of atherosclerotic cardiovascular disease were randomized to receive placebo over eight weeks or oral 6 mg, 12 mg, 18 mg or 30 mg MK-0616 once daily.They were followed up for another eight weeks.
The primary efficacy endpoint was the percentage change in LDL cholesterol from baseline to week 8. Secondary endpoints were percentage change in apolipoprotein B-100 (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 8 and the proportion of participants who met the LDL cholesterol goals defined in the protocol at week 8.
At all doses, MK-0616 significantly reduced LDL cholesterol levels at week 8 compared to placebo. The placebo-adjusted LDL cholesterol reduction from baseline was 41.2% for 6 mg, 55.7% for 12 mg, 59.1% for 18 mg, and 60.9% for 30 mg (p <0.001 for all doses).
Already in week 2, an almost complete effect was achieved, which lasted over the eight-week treatment period. Results were consistent across all predefined subgroups
At week 8, secondary endpoints were also significantly improved with all MK-0616 doses compared to placebo: ApoB levels were reduced between 32.8% (6 mg) and 51.8% (30 mg), non-HDL cholesterol levels were decreased by 35.9% (6 mg) to 55.8% (30 mg), and LDL cholesterol goals were met by 80.5% (6 mg) to 90.8% (30 mg) of patients.
MK-0616 was well tolerated overall.In the verum group, one patient died due to a traffic accident.
This article originally appeared on Medscape.de
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