Regeneron Pharmaceuticals Inc announced that the US Food and Drug Administration (FDA) approved Evkeeza (evinacumab-dgnb) as an adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies to treat adult and pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH). Evkeeza is the first US 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 US 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. "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."
HoFH, also known as homozygous FH, is an ultra-rare inherited condition that affects approximately 1,300 patients in the US. 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 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."
"Evkeeza is the first US FDA-approved ANGPTL3 inhibitor and the latest example of the promise of Regeneron's development approach that harnesses genetic insights and pioneering technology to deliver new treatment options for patients who need them," said George D. Yancopoulos, M.D., Ph.D., president and chief scientific officer at Regeneron. "We are proud to bring Evkeeza to patients with HoFH, and Regeneron is grateful to the patients and doctors who participated in our trials to make this a reality."
The US FDA approval is based on results from the phase 3 ELIPSE HoFH trial. 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% on average compared to placebo at week 24 (47% reduction Evkeeza, 2% increase placebo, p<0.0001).
The US 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 (evinacumab-dgnb) is a fully-human monoclonal antibody that binds to and blocks the function of ANGPTL3. Regeneron scientists discovered the angiopoietin gene family more than two decades ago. Human genetics research published in NEJM in 2017 by scientists from the Regeneron Genetics Center found that patients whose ANGPTL3 gene did not function properly (called a "loss-of function mutation") have significantly lower levels of key blood lipids, including LDL-C, and this is associated with a significantly lower risk of coronary artery disease.