Efficacy for LDL-C–lowering and safety of pemafibrate extended-release formulation in patients with statin-intolerant hypercholesterolemia: A phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group trial

BACKGROUND: Management of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance requires treatment options beyond statins. Pemafibrate, primarily used to lower serum triglycerides in patients with hypertriglyceridemia, has also been reported in some clinical trials to reduce LDL-C. OBJECTIVE: To evaluate the efficacy and safety of pemafibrate in patients with statin-intolerant hypercholesterolemia. METHODS: In this phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, patients with statin-intolerant hypercholesterolemia and normal triglyceride levels were enrolled. The primary endpoint was the percentage change in calculated LDL-C from baseline to week 12. RESULTS: Seventy-one patients were randomly assigned to receive placebo or the extended-release (XR) formulation of pemafibrate at 0.2 mg/d or 0.4 mg/d. LDL-C decreased significantly from baseline in the pemafibrate groups (least squares mean [95% CI]: -20.0% [-24.1 to -15.9] for XR 0.2 mg/d; -24.8% [-28.8 to -20.9] for XR 0.4 mg/d), demonstrating superiority over placebo (-0.4% [-4.2 to 3.5]). Reductions in apolipoprotein B were also greater in the pemafibrate groups than in the placebo group (least squares mean; -18.2% for XR 0.2 mg/d; -20.6% for XR 0.4 mg/d; P < .001 vs placebo). Treatment-emergent adverse events were generally similar across groups, though slightly more frequent in the pemafibrate groups (47.8% for XR 0.2 mg/d and 54.2% for XR 0.4 mg/d) than in the placebo group (37.5%). CONCLUSION: Pemafibrate effectively and safely reduces LDL-C in patients with statin-intolerant hypercholesterolemia and normal triglyceride levels, offering a potential new therapeutic option for this population.