FDA Approves First-in-class Evkeeza (evinacumab-dgnb) for Young Children with Ultra-rare Form of High Cholesterol

Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) has extended the approval of Evkeeza (evinacumab-dgnb) as an adjunct to other lipid-lowering therapies to treat children aged 5 to 11 with homozygous familial hypercholesterolemia (HoFH). Evkeeza is the first angiopoietin-like 3 (ANGPTL3) inhibitor treatment indicated for children as young as 5 years old to control dangerously high levels of low-density lipoprotein cholesterol (LDL-C) caused by HoFH. Evkeeza was initially approved as an adjunct to other lipid-lowering therapies in those aged 12 years and older with HoFH in February 2021.

“At the Family Heart Foundation, we know that children with homozygous familial hypercholesterolemia, and those caring for them, often live in fear of what the future holds as they contend with the dangerously high levels of bad cholesterol, or LDL-C, caused by this genetic disorder,” said Mary McGowan, M.D., Chief Medical Officer of the Family Heart Foundation. “Only 5% of rare diseases actually have an FDA-approved treatment. With this FDA approval, the HoFH community now has a much-needed treatment for young children, potentially making it possible for many to achieve recommended LDL-C levels much earlier in the course of this rare disease. This is a hopeful development for those living with HoFH.”

HoFH is an ultra-rare inherited condition that affects approximately 1,300 people in the U.S. and is the most severe form of familial hypercholesterolemia (FH). HoFH 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 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.

“Guidelines recommend screening all children at high risk for homozygous familial hypercholesterolemia starting at age 2. However, until now, a positive diagnosis was often met with the frustration of having limited treatment options to help these children,” said Carissa M. Baker-Smith, M.D., MPH, Co-Director of Nemours Cardiac Center Cardiovascular Research and Innovation Program, Director of Nemours Cardiac Center Pediatric Preventive Cardiology, pediatric cardiologist, and a trial investigator. “By adding Evkeeza to standard lipid-lowering therapies in this pivotal trial, children were able to reduce their LDL-C, with the vast majority able to achieve declines of nearly 50%. These are clinically meaningful results that physicians should consider when developing a treatment approach for these young patients.”

Despite treatment with other lipid-lowering therapies, children entered the Phase 3 trial with an average LDL-C level of 264 mg/dL, more than twice the target (<110 mg/dL) for pediatric patients with HoFH. With the addition of Evkeeza, children were able to reduce their LDL-C by 48% at week 24 on average, meeting the trial’s primary endpoint. Significant reductions were also observed in other key secondary endpoints including levels of apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C) and total cholesterol.

The safety profile of Evkeeza observed in these patients (n=20) was consistent with the safety profile observed in adults and pediatric patients aged 12 years and older, with the additional adverse reaction of fatigue. Fatigue was reported in 3 (15%) patients. The most common adverse events (AEs) occurring in >15% of patients were COVID-19 (n=15), pyrexia (n=5), headache (n=4), throat pain (oropharyngeal pain, n=4) as well as upper abdominal pain, diarrhea, vomiting, fatigue, nasopharyngitis, rhinitis and cough (all n=3). Most reported AEs were mild or moderate, and none led to study discontinuation.

“Since it was first approved, Evkeeza has become the standard of care for homozygous familial hypercholesterolemia in those aged 12 years or older. We’re gratified that now children as young as 5 years old have the potential to benefit from this treatment,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. “As a first-in-class medicine for this relentless disease, Evkeeza exemplifies the promise of genetics-based research to transform treatment paradigms. Evkeeza’s journey from target discovery to treatment innovation was only made possible due to our long-term investment in genetics research and monoclonal antibody technologies, and this remains a central tenet of our science-first approach to this day.”

Regeneron is committed to helping patients who have been prescribed Evkeeza access their medication. Regeneron’s myRARE™ patient support program offers financial assistance to eligible patients who need help with the out-of-pocket cost of Evkeeza. Under the program, eligible patients with commercial insurance may pay as little as $0 in out-of-pocket costs for Evkeeza. In addition, myRARE™ offers resources to help patients and healthcare providers get started with Evkeeza including product information, insurance benefit verification, community resources and appointment reminders.

The FDA evaluated the supplemental biologics license for Evkeeza in this indication under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.

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.