FDA Approves Regeneron’s Evkeeza for Patients with Ultra-Rare Form of High Cholesterol

Rare Daily Staff

The U.S. Food and Drug Administration approved Evkeeza as an adjunct to other low-density lipoprotein cholesterol lowering therapies to treat adult and pediatric patients 12 years and older with homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH or FH) is an ultra-rare inherited condition that affects approximately 1,300 patients in the U.S. and is characterized by extremely high low-density lipoprotein cholesterol (LDL-C). HoFH occurs when two copies of the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of LDL-C (bad cholesterol). Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years.

Evkeeza is the first FDA-approved treatment that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that plays a key role in lipid metabolism.

“The FDA’s approval of Evkeeza is a watershed moment for individuals born with HoFH, a severe form of familial hypercholesterolemia,” said Katherine Wilemon, founder and CEO of the FH Foundation. “Those living with HoFH have faced devastatingly high LDL-C levels and an uncertain future. Evkeeza significantly lowered LDL-C levels in clinical trials and this new treatment offers an important new option for people living with HoFH.”

The FDA approval is based on results from the phase 3 ELIPSE HoFH trial, published in the New England Journal of Medicine in August 2020. In the trial, 65 patients were randomized to receive either Evkeeza 15 mg/kg intravenously every four weeks (n=43) plus other lipid-lowering therapies, compared to lipid-lowering therapies alone (placebo, n=22). The mean baseline LDL-C level of patients in both groups was 255 mg/dL.

The trial met its primary endpoint, with Evkeeza-treated patients reducing their LDL-C from baseline by 49 percent on average compared to placebo at week 24. At the same time point, compared to baseline, Evkeeza-treated patients also experienced 132 mg/dL average reduction in LDL-C compared to placebo. Reductions in LDL-C seen with Evkeeza were observed as early as week 2 and maintained throughout the double-blind treatment period (week 24) and open label trial period (through week 48).

Significant reductions were also observed in other key secondary endpoints including levels of apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C) and total cholesterol, compared to placebo. Similar levels of LDL-C lowering were also observed in the most difficult-to-treat patients who often don’t respond to certain other therapies because of limited LDL receptor function.

The most common adverse reactions (>3% of patients) reported from the combined safety analysis of placebo-controlled trials after 24 weeks that occurred more frequently in Evkeeza patients (n=81) than placebo (n=54) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, pain in extremity, and asthenia. In clinical trials, adverse reactions led to discontinuation of treatment in 2 percent of patients treated with Evkeeza, including 1 case of anaphylaxis that resolved with treatment, and 2 percent of patients who received placebo.

Evkeeza is a fully human monoclonal antibody that binds to and blocks the function of ANGPTL3 and is administered based on weight (15 mg/kg) once a month via intravenous infusion.

Regeneron expects to price it at approximately $450,000 per year on average and has a patient support program that offers financial assistance to eligible patients who need help with the out-of-pocket costs.

The FDA evaluated Evkeeza under Priority Review, following the decision in 2017 to grant Evkeeza Breakthrough Therapy designation for the treatment of hypercholesterolemia in patients with HoFH.

“Evkeeza is a potentially transformational new treatment for people with HoFH,” said Daniel Rader, professor and chair of the Department of Genetics in the Perelman School of Medicine of the University of Pennsylvania, and a leading HoFH expert who was involved with Evkeeza clinical trials. “Existing therapies for HoFH are insufficient for the majority of patients. Evkeeza, 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.”