New oral PCSK9 inhibitor lowers LDL-c in hypercholesterolemia

News - Mar. 8, 2023

Efficacy and Safety of the Oral PCSK9 Inhibitor, MK-0616, A Macrocyclic Peptide, in the Treatment of Hypercholesterolemia: A Phase 2b Randomized Placebo-Controlled Clinical Trial

Presented at the ACC.23/WCC by: Christie Ballantyne, MD - Houston, TX, USA

Introduction and methods

The current PCSK9 inhibitors have shown to lower LDL-c and reduce risk of ASCVD, but these injectables treatment with access barriers and the need for repeat injections have led to poor adoption.

In the phase 2b study, the effect of the oral, macrocyclic PCSK9 inhibitor MK-0616 on the change in LDL-c from baseline to week 8 was examined in 381 patients with hypercholesterolemia (39% had clinical ASCVD).

Doses of 6, 12, 18 and 30 mg of MK-0616 were compared to placebo.

The primary efficacy endpoint was LDL-c reduction from baseline to week 6 and the safety endpoints were adverse events (AEs) and discontinuation due to AEs.

Main results

Efficacy

LDL-c was reduced with all doses of MK-0616 (placebo-adjusted % LDL-c reductions were -41.2 [-47.8 to -34.7], -55.7 [-62.3 to -49.1], -59.1 [-65.7 to -52.5], -60.9 [-67.6 to -54.3] for 6, 12, 18 30 mg, respectively, P<0.001).
Reductions of ApoB (up to 51.8%) and non-HDL-c (up to 55.8%) were also observed.
Proportions of participants that achieved protocol-specified LDL-c goals were larger in the MK-0616 groups (80.5-90.8%) than in the placebo arm (9.3%).

Safety

AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5-43.3%) and the placebo arm (44.0%).
Discontinuation due to AEs occurred in ≤2 participants in any treatment group.

Conclusion

This phase 2b RCT in a diverse population of patients with hypercholesterolemia, all doses of MK-0616 significantly reduced LDL-c when compared to placebo at 8 weeks. Secondary efficacy endpoints were supportive of the findings of the primary efficacy endpoint. Moreover, MK-0616 was well tolerated, without a trend in AEs across treatment groups.

- Our reporting is based on the information provided at the ACC.23/WCC -

Watch a video by prof. Ballantyne The findings of this study were simultaneously published in J Am Coll Cardiol