ANGPTL3 inhibitor approved by FDA for patients with HoFH
The US Food and Drug Administration (FDA) approved evinacumab as an adjunct to other LDL-c lowering therapies for the treatment of patients ≥12 years with homozygous familial hypercholesterolemia (HoFH). Evinacumab binds to and inhibits the function of angiopoietin-like 3 (ANGPTL3).
The approval is based on results from the phase 3 ELIPSE HoFH trial. 65 Patients in this trial were randomized to evinacumab (IV every four weeks, n=43) or placebo (n=22). In patients treated with evinacumab, LDL-c was reduced by 49% compared to patients on placebo at week 24 (P<0.0001). In addition, key secondary endpoints (apoB, non-HDL-c and total cholesterol) were reduced compared to placebo (P<0.0001). In patients with limited LDL receptor function (‘null/null’ or ‘negative/negative’) similar levels of LDL-c lowering were observed.
The most common adverse reactions that occurred more frequently in evinacumab-treated patients than in those who received placebo were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, pain in extremity and asthenia. Adverse reactions leading to discontinuation of treatment occurred in 2% of patients treated with evinacumab and 2% of patients on placebo.
Regulatory review for evinacumab is ongoing in the EU. In June 2020, the CHMP of EMA recommended accelerated assessment for evinacumab based on the high unmet medical need and the therapeutic innovation.
Daniel J. Rader, M.D., Professor and Chair of the Department of Genetics in the Perelman School of Medicine of the University of Pennsylvania: "Existing therapies for HoFH are insufficient for the majority of patients. Evinacumab, through its unique mechanism of action, was shown to reduce LDL-C levels in patients with all forms of HoFH, even those with nearly no LDL receptor activity, and represents a highly meaningful improvement in our ability to control LDL-C levels in patients with HoFH."