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Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy

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posted on 03.03.2022, 15:06 by Henry N. Ginsberg, Neil J. Hounslow, Yusuke Senko, Hideki Suganami, Pawel Bogdanski, Richard Ceska, Akos Kalina, Roman A. Libis, Tatiana V. Supryadkina, G. Kees Hovingh
Background High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG-levels through PPARα agonism. Currently available fibrates, however, have relatively low selectivity for PPARα.

Objectives The aim of this trial was to assess the safety, tolerability and efficacy of K-877 (pemafibrate) —a selective PPARα modulator —in statin-treated European patients with hypertriglyceridemia.

Methods A total of 408 statin-treated adults were recruited from 68 European sites for this Phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-C ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomized to receive placebo or one of 6 pemafibrate regimens: 0.05 mg BID, 0.1 mg BID, 0.2 mg BID, 0.1 mg QD, 0.2 mg QD, or 0.4 mg QD. The primary endpoints were TG and non-HDL-C level lowering at Week 12.

Results

Pemafibrate reduced TG at all doses (adjusted p value <0.001) with the greatest placebo-corrected reduction from baseline to Week 12 observed in the 0.2 mg BID treatment group (54.4%). Reductions in non-HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol, and an increase in HDL-C levels. Pemafibrate increased LDL-C levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations.

Conclusion

Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.

Funding

This study was sponsored by Kowa Research Europe Ltd, an affiliate of Kowa Company Ltd, Tokyo, Japan.

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