Oral PCSK9 inhibitor effectively lowers LDL-c
The Clinical Safety, Pharmacokinetics, and LDL-Cholesterol Lowering Efficacy of MK-0616, an Oral PCSK9 Inhibitor
Presented at the American Heart Association’s Scientific Sessions 2021 by: Douglas Johns, PhD - Kenilworth, NJ, USA
Introduction and methods
Aim of the study
Injectable PCSK9 inhibitors reduce LDL-c levels by ~50-60%. However, the clinical uptake of these injectable agents has been limited and they are often initiated relatively late in a patient’s treatment journey. The development of oral PCSK9 inhibitors has been challenging. Douglas Johns, PhD presented the results of two phase I clinical trial that investigated the efficacy, safety and pharmacokinetics of MK-0616, an orally bioavailable PCSK9 inhibitor.
The first single dose study randomized 60 healthy male volunteers aged 18-50 years in a 3:1 ratio to receive a single dose of MK-0616 (10-300 mg) or placebo. This study investigated the safety of MK-0616 and effects of this agent on free plasma PCSK9 levels.
The second trial was a multidose study which enrolled 40 male and female participants aged 18-65 years who had hypercholesterolemia (baseline LDL-c 60-160 mg/dL) while on statin therapy for at least 3 months, but were otherwise healthy. Participants in the second trial were randomized in a 3:1 ratio to receive MK-0616 (10 or 20 mg) or placebo once a day for 14 days. This trial assed the effect of MK-0616 on LDL-c levels.
- The single dose study showed that a single dose of MK-0616 was well tolerated and no adverse events were observed. All doses of MK-0616 lowered free PCSK9 in the blood by more than 90%, compared to baseline.
- The multidose study found that both 10 and 20 mg doses of MK-0616 on top of statin therapy reduced LDL-c levels by ~65% at day 14, compared to baseline.
- Having a meal before prior to MK-0616 dosing caused an attenuation of absorption and resulted in sub-maximal LDL-c lowering.
These phase I studies provide first in-human clinical data that support the safety and LDL-c-lowering effects of an oral PCSK9 inhibitor. Douglas Johns, PhD acknowledged that additional larger clinical trials will be required to confirm the safety and efficacy of MK-0616.
-Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021-