The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for evinacumab (Regeneron) as an adjunct to other lipid-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH).
Evinacumab is an investigational fully-human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3) using the Company’s proprietary VelocImmune® technology. ANGPTL3 acts as an inhibitor of lipoprotein lipase and endothelial lipase, and appears to play a central role in lipoprotein metabolism.
The BLA submission is supported by data from the double-blind, placebo-controlled phase 3 ELIPSE HoFH trial that evaluated the efficacy and safety of evinacumab in 65 patients aged ≥12 years with HoFH. Patients were randomized 2:1 to receive either evinacumab 15mg/kg intravenously every 4 weeks or placebo. In the evinacumab treatment arm, patients were on the following lipid-lowering therapies: statins (98%), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (81%), ezetimibe (75%), LDL apheresis (33%), lomitapide (26%). The primary end point was the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to week 24.
Results showed that at week 24, patients treated with evinacumab had a 47% reduction in LDL-C compared with a 2% increase for patients treated with placebo (absolute change in LDL-C from baseline was 132mg/dL; P <.0001). Moreover, 47% of patients in the evinacumab arm achieved LDL-C levels of <100mg/dL (average baseline LDL-C level was 260mg/dL) compared with 23% in the placebo arm (nominal P =.0203).
In addition, the study met key secondary end points with 84% and 56% of patients in the evinacumab arm achieving at least 30% and 50% reductions, respectively, in LDL-C levels compared with 19% and 5% for placebo, respectively (P <.0001 and P =.0003). Evinacumab was also associated with statistically significant reductions in levels of apolipoprotein B, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides, compared with placebo (P <.0001 for all).
As for safety, evinacumab was generally well tolerated with the most common adverse events being influenza-like illness (11% evinacumab vs 0% placebo) and rhinorrhea (7% evinacumab vs 0% placebo).
A Prescription Drug User Fee Act (PDUFA) target date of February 11, 2021 has been assigned to this application.
For more information visit regeneron.com.
- FDA accepts evinacumab Biologics License Application for Priority Review as a treatment for patients with HoFH, an ultra-rare inherited form of high cholesterol. https://www.prnewswire.com/news-releases/fda-accepts-evinacumab-biologics-license-application-for-priority-review-as-a-treatment-for-patients-with-hofh-an-ultra-rare-inherited-form-of-high-cholesterol-301110441.html. Accessed August 12, 2020.
- Regeneron announces American College of Cardiology presentation of positive phase 3 evinacumab results in patients with severe inherited form of high cholesterol. https://investor.regeneron.com/index.php/news-releases/news-release-details/regeneron-announces-american-college-cardiology-presentation. Accessed August 12, 2020.