Evkeeza (evinacumab-dgnb) ANGPTL3 antibody approved by FDA for children as young as one year old with homozygous hypercholesterolemia – Regeneron

Regeneron Pharmaceuticals, Inc. announced that the FDA has approved Evkeeza (evinacumab-dgnb) ANGPTL3 antibody as an adjunct to diet and exercise and other lipid-lowering therapies for the treatment of children from age 1 to less than 5 years old with homozygous familial hypercholesterolemia (HoFH). Evkeeza was initially approved in 2021 for adults and adolescents aged 12 years and older with HoFH based on a placebo-controlled trial showing Evkeeza, when added to standard lipid-lowering therapies, could lower LDL-C by about 50% compared to placebo in this high unmet need population. It was then approved for children aged 5 to 11 in 2023. All Evkeeza FDA submissions were evaluated under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.

HoFH is the most severe form of familial hypercholesterolemia (FH), and affects approximately 1,300 people in the U.S. It occurs when two copies of the FH-causing genes are inherited, one from each parent, resulting in dangerously high levels (usually >400 mg/dL) of low-density lipoprotein cholesterol (LDL-C). Those living with HoFH are at risk for premature atherosclerotic disease and cardiac events even in their teenage years. Many patients are not diagnosed or are only diagnosed later in life.

“The approval of Evkeeza for children as young as 1 year of age addresses a critical unmet need for those with homozygous familial hypercholesterolemia, a life-threatening condition that causes extraordinarily high LDL-C levels from birth,” said Katherine Wilemon, Founder and CEO of the Family Heart Foundation. “Families and their medical teams will now have an effective treatment option for these very young children who are at risk of serious complications from diseased arteries and calcified valves without timely and sufficient LDL-C lowering. This development underscores the importance of, and urgency needed in, identifying children with FH through pediatric screenings in accordance with guidelines.”

The extended indication for Evkeeza was supported by clinical efficacy and safety data among 6 children living with HoFH (including pharmacokinetic data among 4 of these patients) who took part in either the U.S. expanded access program or ex-U.S. compassionate use program for Evkeeza. No new safety concerns have been identified in the compassionate use program. The most common adverse reactions (≥5%) of Evkeeza include nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, and fatigue.

“Evkeeza is a testament to the power of Regeneron’s science and proprietary technologies in developing first-in-class, lifechanging medicines that become standard-of-care,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. “This label extension adds to our growing commitment to the rare disease space, which includes diverse clinical development programs in neuromuscular and genetic diseases – such as myasthenia gravis, otoferlin hearing loss, and fibrodysplasia ossificans progressiva – for which we’ve shared data.”

The pharmacokinetics and efficacy of the drug in pediatric patients aged 6 months to less than 5 years with HoFH have been predicted from a model-based extrapolation analysis. Results of these analyses show that pediatric patients aged 6 months to less than 5 years are predicted to experience a similar or higher magnitude of percent change in LDL-C at week 24 compared to older pediatric patients and adults, when receiving a 15 mg/kg dose every 4 weeks. In addition, supportive data for five patients who initiated treatment between 1 and 4 years of age via compassionate use showed a clinically meaningful reduction of LDL-C consistent with that observed in patients aged 5 years or older in clinical studies. Based on the currently available data, the safety profile in pediatric patients aged 6-months to 5 years old is expected to be similar to the safety profile in older pediatric patients. No new safety concerns have been identified in the compassionate use program.

Evkeeza is reimbursed and clinically available to prescribe for appropriate patients with HoFH in Canada via private drug plans and via the public drug program in Quebec, the UK, U.S., Italy, Japan, the Netherlands, Spain and Luxembourg. It is also available via early access programs in 13 additional countries including Austria and France.