Long-Term Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor-α Modulator (SPPARMα), in Dyslipidemic Patients with Renal Impairment

• Main Authors: Koutaro Yokote, Shizuya Yamashita, Hidenori Arai, Eiichi Araki, Hideki Suganami, Shun Ishibashi, on Behalf of the K-877 Study Group
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: International Journal of Molecular Sciences
• Subjects: high-density lipoprotein cholesterol; K-877; pemafibrate; renal dysfunction; safety; selective PPARα modulator; triglyceride
• Online Access: https://www.mdpi.com/1422-0067/20/3/706

Pemafibrate (K-877) is a novel selective peroxisome proliferator-activated receptor-α modulator (SPPARMα) with a favorable benefit-risk balance. Previous clinical trials of pemafibrate used stringent exclusion criteria related to renal functions. Therefore, we investigated its safety and efficacy in a broader range of patients, including those with chronic kidney disease (CKD). In this multicenter, single-arm, open-label, phase III trial, 0.2–0.4 mg/day pemafibrate was administered for 52 weeks to 189 patients with hypertriglyceridemia and an estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m² on statin or regardless of eGFR when statin was not administered. Post-hoc analyses were performed on subgroups stratified by baseline eGFR. Triglyceride levels decreased by 45.9% at week 52 (last-observation-carried-forward). These reductions were not correlated with baseline eGFR. The eGFR < 30 mL/min/1.73 m² subgroup showed the greatest reduction in chylomicron, very low-density lipoprotein, small low-density lipoprotein cholesterol levels, and an increase in high-density lipoprotein cholesterol levels. The incidences of adverse events and adverse drug reactions were 82.0% and 31.7%, respectively, and these were not associated with baseline eGFR. In CKD patients, pemafibrate blood concentrations were not elevated. Pemafibrate showed a good safety profile and efficacy in correcting lipid abnormalities in a broad range of patients, including those with CKD.