The U.S. Food and Drug Administration (FDA) has approved Evkeeza (evinacumab-dgnb) to treat persons 12 years and older with homozygous familial hypercholesterolemia (HoFH).
Evinacumab-dgnb is a monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein involved in lipid metabolism. Two other drugs currently available and approved to treat HoFH are evolocumab and lomitapide. Evolocumab binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) while lomitapide binds and inhibits microsomal triglyceride transfer protein (MTP).
HoFH is a genetic disorder that results in severe impairment of the low-density lipoprotein receptor (LDL-R). The end result is extremely high levels of LDL-cholesterol (LDL-C), (e.g., > 400 mg/dL or 10mmol/L,} that is very difficult, if not impossible, to control with standard lipid lowering strategies. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years.
The FDA approval is largely based on results from the Phase 3 ELIPSE HoFH trial, published in the New England Journal of Medicine in August 2020. In that trial, 65 patients with HoFH were randomized to receive evinacumab 15 mg/kg intravenously every four weeks (n=43) plus other lipid-lowering therapies, or lipid-lowering therapies alone (n=22).
The trial met its primary endpoint, with evinacumab-treated patients reducing their LDL-C from baseline by 47% compared to a 2% increase seen in the placebo group, P < .0001).
The most common adverse reactions (>3% of patients) were nasopharyngitis, influenza-like, dizziness, rhinorrhea, nausea, pain in extremity, and asthenia.
The drug is administered based on weight (15 mg/kg) once a month via intravenous infusion. The average Wholesale Acquisition Cost (WAC) per patient in the U.S. will vary based on weight, but the expected average cost will be approximately $450,000 per year.
In an exclusive interview with CheckRare, James Underberg MD, Clinical Assistant Professor of Medicine at NYU Medical School, describes HoFH and what the treatment options are for this very rare condition.
James Underberg, MD provides an overview of HoFH
James Underberg, MD reviews the treatment options for HoFH
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