FDA Approves Evinacumab-dgnb for Young Children With Homozygous Familial Hypercholesterolemia


Evinacumab-dgnb (Evkeeza; Regeneron Pharmaceuticals, Inc) is the first FDA-approved treatment indicated for children as young as 5 years of age to treat dangerously high levels of LDL-C.

Officials with the FDA have extended the approval for evinacumab-dgnb (Evkeeza; Regeneron Pharmaceuticals, Inc) as an adjunct to other lipid-lowering drugs for children 5 to 11 years of age with homozygous familial hypercholesterolemia (HoFH). Evinacumab-dgnb was approved in February 2021 as an adjunct to other treatments that reduce low-density lipoprotein cholesterol (LDL-C) in patients aged 12 years and older with HoFH.

Evinacumab-dgnb is the first FDA-approved treatment that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that plays a key role in lipid metabolism, and it is the first treatment indicated for children as young as 5 years of age to treat dangerously high levels of LDL-C.

“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, MD, chief medical officer of the Family Heart Foundation, in a press release. “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, also known as homozygous FH, is an ultra-rare inherited condition that affects approximately 1300 patients in the United States. The condition occurs when 2 copies of the FH-causing genes are inherited, 1 from each parent, resulting in dangerously high levels (>400 mg/dL) of LDL-C. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years.

Patients with HoFH are at risk for developing premature atherosclerotic disease and cardiac events in their teenage years, many of whom 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,” trial investigator Carissa M. Baker-Smith, MD, MPH, co-director of Nemours Cardiac Center Cardiovascular Research and Innovation Program, director of Nemours Cardiac Center Pediatric Preventive Cardiology, pediatric cardiologist, said in a press release. “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.”

Evinacumab-dgnb was evaluated in a 3-part, single-arm, open-label trial in which the drug was added to other lipid-lowering therapies in patients 5 to 11 years of age with HoFH. Part A (n=6) was a phase 1b trial that evaluated the pharmacokinetics, safety, and tolerability of the drug. Part B (n=14) analyzed the efficacy of evinacumab-dgnb over a 24-week treatment period with patients at an average of 9 years of age. Of these patients, 86% were on statins, 93% were on ezetimibe, 50% were on LDL apheresis, and 14% were on lomitapide. Patients were administered evinacumab-dgnb 15 mg/kg every 4 weeks intravenously with their lipid-lowering treatment regimen.

The trial’s primary endpoint was change in LDL-C at week 24 and secondary endpoints included the effect of evinacumab-dgnb on other lipid parameters—such as apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein[a], and total cholesterol­—as well as efficacy by mutation status, safety and tolerability, immunogenicity, and PK.

Even with having received treatment other lipid-lowering drugs, patients enrolled in the phase 3 trial had an average LDL-C level of 264 mg/dL, which is more than twice the target (<110 mg/dL) for pediatric patients with HoFH. After treatment with evinacumab-dgnb, these patients experienced a drop in LDL-C by 48% at week 24 on average, which achieved the primary endpoint. There were also significant declines in other key secondary endpoints, including levels of apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol, and total cholesterol.

The safety profile of evinacumab-dgnb was consistent with what was observed in adults and pediatric patients 12 years of age and older. In addition to the adverse events (AEs) previously noted, fatigue was a newly reported AE associated with treatment and was observed in 3 (15%) patients.

The most common AEs occurring in >15% of patients were COVID-19 (n=15), pyrexia (n=5), headache (n=4), and throat pain (oropharyngeal pain, n=4). AEs of upper abdominal pain, diarrhea, vomiting, fatigue, nasopharyngitis, rhinitis, and cough (all n=3) were also reported. Most of the AEs were mild or moderate and none led to discontinuation of evinacumab-dgnb.

The safety and efficacy of evinacumab-dgnb have not been established in patients with other causes of hypercholesterolemia, including heterozygous familial hypercholesterolemia, and the effect of the drug on cardiovascular morbidity and mortality has not yet been determined.

“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, MD, PhD, president and chief scientific officer at Regeneron, in a press release. “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.”


FDA approves first-in-class Evkeeza® (evinacumab-dgnb) for young children with ultra-rare form of high cholesterol. Regeneron. News release. March 22, 2023. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-first-class-evkeezar-evinacumab-dgnb-young-children

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