Alirocumab, Evinacumab Reduce LDL-C Levels in Adults with HoFH

PCSK9 inhibitors alirocumab and novel evinacumab significantly reduced LDL-C levels in adults with homozygous familial hypercholesterolemia (HoFH), according to science presented at ACC.20/WCC virtual meeting.

Results come from two phase 3 studies. The ODYSSEY HoFH placebo-controlled trial tested the efficacy of alirocumab and found that after 12 weeks, LDL-C levels were 26.9% lower in the alirocumab group compared with 8.6% higher in the placebo group. The study also showed it is well-tolerated and reported no treatment-related adverse events.

“This trial is the largest randomized controlled interventional trial in adults with HoFH to date and offers important insights into the disease,” explained Dirk Blom, MD, PhD, the study’s lead author. “Alirocumab is a potential new therapy that should be considered in appropriate patients with HoFH. Unfortunately, there is also a small number of patients with specific mutations who do not respond, or only respond very poorly, to alirocumab.”

Per a press release from ACC, the second trial “examined the investigational evinacumab, also a monoclonal antibody, which binds to angiopoietin-like protein 3 (ANGPTL3). By targeting ANGPTL3, evinacumab is designed to reduce LDL-C through a different mechanism than any existing drug.”

Results showed significantly reduced LDL-C levels, beginning in the second week in patients treated with evinacumab. At week 24, average LDL-C levels had been reduced by 47.1% while the placebo group’s LDL-C levels rose by 1.9%.

“For the first time, we were able to get these patients with HoFH to remarkably normal LDL-C levels,” said Frederick J Raal, PhD, lead author of the phase 3 trial testing evinacumab. “It’s the most potent cholesterol-lowering drug we’ve seen for this very difficult-to-treat group of patients.” —Edan Stanley