In this double-blind, placebo-controlled, phase III ELIPSE HoFH trial, Raal et al randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to obtain an IV infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo.
The primary outcome was the percent shift from baseline in the LDL cholesterol level at week 24. The researchers found that average baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, in spite of the receipt of highest doses of background lipid-lowering therapy. At Week 24, patients in the evinacumab group had a relative decrease from baseline in the LDL cholesterol level of 47.1%, compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean variance of –49.0 percentage points (95% confidence interval [CI], –65.0 to –33.1; P <.001); the between-group least-squares average absolute variance in the LDL cholesterol level was –132.1 mg per deciliter (95% CI, –175.3 to –88.9; P <.001).
The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null–null variants (–43.4% vs. +16.2%) and in those with nonnull variants (–49.1% vs. –3.8%). Among the two groups, the adverse events were comparable. Raal et al concluded that in patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the decrease from baseline in the low-density lipoprotein (LDL) cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks.
On August 12, 2020, the FDA accepted for Priority Review a Biologics License Application (BLA) for evinacumab as an adjunct to other lipid-lowering therapies in patients with HoFH. Evinacumab is the first investigational medicine of its kind to demonstrate efficacy in patients with HoFH, including patients with little to no LDL receptor function. The BLA was supported by the pivotal phase III trial mentioned above. Results from this trial were presented as a late-breaking presentation at the American College of Cardiology's Annual Scientific Session together with the World Congress of Cardiology in March 2020. The target action date for the FDA decision is February 11, 2021. The FDA granted evinacumab Breakthrough Therapy designation in 2017 for the treatment of hypercholesterolemia in patients with HoFH.
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