FDA approves evinacumab for homozygous FH
Regeneron announced the FDA has approved evinacumab for treatment of patients aged 12 years or older with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies.
According to a press release from the company, evinacumab (Evkeeza), a human monoclonal antibody, is a first-in-class drug that binds to and blocks angiopoietin-like 3 (ANGPTL3). Various ANGPTL3 inhibitors are in development but none had been approved until now.
Homozygous familial hypercholesterolemia (HoFH) is a rare but serious condition affecting approximately 1,300 people in the United States, who often have LDL levels greater than 400 mg/dL and can have atherosclerosis and cardiac events as early as adolescence, according to the release.
“We don’t have the entire answer on the drug’s mechanism of action, We do know that ANGPTL3 under normal circumstances inhibits both lipoprotein lipase and endothelial lipase. We de-repress this with the administration of evinacumab. Greater activity of lipoprotein lipase increases metabolism of VLDL particles. This may lead to decreased production of LDL,” Cardiology Today Editorial Board Member Seth J. Baum, MD, FACC, FAHA, FNLA, FASPC, founder and chief medical officer of Excel Medical Trials, LLC, and clinical affiliate professor of biomedical science in the department of integrated medical sciences at the Florida Atlantic University Charles E. Schmidt College of Medicine, told Healio. “Another mechanism of action relates to endothelial lipase. De-repression of endothelial lipase modifies LDL particles and may enhance LDL catabolism through LDL receptor-independent pathways.”
Approval was based on the ELIPSE HoFH trial, in which patients with HoFH assigned evinacumab had a 49% reduction in LDL, as well as reductions in apolipoprotein B, non-HDL and total cholesterol, compared with those assigned placebo, the company stated in the release.
“Evkeeza is a potentially transformational new treatment for people with HoFH,” Daniel J. Rader, MD, professor and chair of the department of genetics in the Perelman School of Medicine of the University of Pennsylvania, who was involved with trials of the drug, said in the release. “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.”
Katherine A. Wilemon, founder and CEO of the FH Foundation, said in the release that the approval is a “watershed moment” for patients with HoFH.
“Those living with HoFH have faced devastatingly high LDL-C levels and an uncertain future,” she said. “Evkeeza significantly lowered LDL-C levels in clinical trials and this new treatment offers an important new option for people living with HoFH.”
Baum told Healio that existing lipid-lowering therapies are not as effective in patients with HoFH as they are in other patients, so a drug that lowers LDL in HoFH should be very helpful, especially in patients with no LDL receptor activity.
“In a post hoc analysis, there was a 72% reduction in LDL in the ‘null-null receptor’ population,” he said. “All things considered, this is an enormous benefit to the HoFH population. The approval will dramatically change the management and care of these patients.”
For more information:
Seth J. Baum, MD, FACC, FAHA, FNLA, FASPC, can be reached at firstname.lastname@example.org