Phase III results for REGN 1500 meets primary endpoint in homozygous familial hypercholesterolemia

Regeneron Pharmaceuticals announced positive pivotal Phase III results for REGN 1500 (evinacumab), an investigational angiopoietin-like 3 (ANGPTL3) antibody, in patients with homozygous familial hypercholesterolemia (HoFH). Patients with HoFH have severely elevated levels of bad cholesterol (otherwise known as low-density lipoprotein cholesterol, or LDL cholesterol), and often experience early atherosclerotic disease, sometimes suffering cardiac events as early as their teenage years. On average, patients entered the trial with LDL cholesterol levels of 255 mg/dL, despite treatment with other lipid-lowering therapies, including maximally-tolerated statins, PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, ezetimibe, LDL apheresis and lomitapide. The trial met its primary endpoint, showing that adding evinacumab to other lipid-lowering therapies decreased LDL cholesterol by 49% on average, compared to lipid-lowering therapies alone.

Results from the evinacumab group at week 24 included a 49% reduction in LDL cholesterol from baseline, compared to placebo (47% reduction for evinacumab compared to a 2% increase for placebo, p<0.0001), the primary endpoint. In addition it produced a 132 mg/dL absolute change in LDL cholesterol from baseline, compared to placebo (135 mg/dL reduction for evinacumab compared to a 3 mg/dL reduction for placebo, p<0.0001). Forty seven per cent achieved LDL cholesterol levels less than 100 mg/dL, compared to 23% for placebo (nominal p=0.0203). Similar levels of LDL cholesterol-lowering were also observed in the most difficult-to-treat patients who often don't respond to certain other therapies, described as "null/null" or "negative/negative" patients. Evinacumab also reduced apolipoprotein B (ApoB), non-HDL cholesterol and total cholesterol compared to placebo. LDL cholesterol reductions were observed from the first assessment at week 2, and were maintained throughout the 24-week double-blind treatment period. In the trial, evinacumab was generally well-tolerated.