Evinacumab gets FDA nod for treatment of rare homozygous FH in children
USA: The U.S. Food and Drug Administration (FDA) has given its approval to Regeneron's evinacumab (Evkeeza) as an adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies. It is indicated for the treatment of adult and pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).
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.
HoFH, also known as homozygous FH, is an ultra-rare inherited condition that affects approximately 1,300 patients in the U.S. 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.
"The FDA's approval of Evkeeza is a watershed moment for individuals born with HoFH, a severe form of familial hypercholesterolemia," said Katherine A. Wilemon, Founder and CEO of the FH Foundation said in a statement. "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 (NEJM) 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.
Key findings include:
- The trial met its primary endpoint, with Evkeeza-treated patients reducing their LDL-C from baseline by 49% on average compared to placebo at week 24 (47% reduction Evkeeza, 2% increase placebo).
- At the same time point, compared to baseline, Evkeeza-treated patients also experienced:
- 1322 mg/dL average reduction in LDL-C compared to placebo (135 mg/dL reduction Evkeeza, 3 mg/dL reduction placebo).
- 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, described as "null/null" (<15% LDL receptor function by in vitro assays) or "negative/negative" (genetic variants likely to result in minimal to no LDL receptor function by mutation analysis) patients.
- 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).
- 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 (16% Evkeeza, 13% placebo), influenza-like illness (7% Evkeeza, 6% placebo), dizziness (6% Evkeeza, 0% placebo), rhinorrhea (5% Evkeeza, 0% placebo), nausea (5% Evkeeza, 2% placebo), pain in extremity (4% Evkeeza, 0% placebo) and asthenia (4% Evkeeza, 0% placebo).
- In clinical trials, adverse reactions led to discontinuation of treatment in 2% of patients treated with Evkeeza, including 1 case of anaphylaxis that resolved with treatment, and 2% of patients who received placebo.
"Evkeeza is a potentially transformational new treatment for people with HoFH," said Daniel J. Rader, M.D., Professor and Chair of the Department of Genetics in the Perelman School of Medicine of the University of Pennsylvania, 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."
The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The effect of Evkeeza on cardiovascular morbidity and mortality has not been determined.
