FDA Makes Landmark Approval for ANGPTL-3 Inhibitors
The U.S. Food and Drug Administration (FDA) approved Regeneron’s monoclonal antibody Evkeeza (evinacumab-dgnb) as an add-on treatment for adult and pediatric patients ages 12 and above with homozygous familial hypercholesterolemia (HoFH). The approval marks the first ANGPTL-3 Inhibitor to be greenlit by the FDA.
Patients with Homozygous FH suffer from dangerously high levels of LDL-C, the “bad” cholesterol. Evkeeza was approved as an adjunct therapy alongside other low-density lipoprotein cholesterol (LDL-C) lowering therapies. As an angiopoietin-like protein 3 inhibitor, Evkeeza plays a central role in lipoprotein metabolism and blocks of lipoprotein lipase and endothelial lipase.
The FDA’s approval of Evkeeza was based on pivotal results from the Phase III ELIPSE trial that demonstrated treatment with Evkeeza nearly halved cholesterol levels after 24 weeks of treatment in patients with HoFH, an ultra-rare inherited disease. Reductions in LDL-C seen with Evkeeza were observed as early as the second week of treatment and were maintained throughout the double-blind treatment period of 24 weeks, Regeneron said. Those results continued to be seen through the open label trial period of 48 weeks, the company added.
The approval was granted under Priority Review. Evkeeza won Breakthrough Therapy Designation from the FDA in 2017 for HoFH.
Homozygous familial hypercholesterolemia affects approximately 1,300 patients in the U.S. The disease occurs when two copies of the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent. This results in dangerously high levels of LDL-C. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years.
George Yancopoulos, president and chief scientific officer of Tarrytown, N.Y.-based Regeneron, said the approval of Evkeeza is 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. He said the company is proud to bring Evkeeza to patients with HoFH.
Evkeeza is administered based on weight (15 mg per kilogram) once a month via intravenous infusion. The average wholesale cost per U.S. patient will vary based on weight, and is expected to be approximately $450,000 per year on average.
Evkeeza was invented using Regeneron's VelocImmune technology, which was also used to create Dupixent, Libtayo, Praluent, Kevzara and other branded drugs.
Katherine A. Wilemon, founder and Chief Executive Officer of the FH Foundation, called the approval of Evkeeza a watershed moment for HoFH patients.
"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,” Wilemon said in a statement.
Daniel J. Rader, chairman 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, called Evkeeza a potentially transformational new treatment.
“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,” Rader said.
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.
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