European Commission Extends Approval of Ultragenyx Evkeeza to Children with HoFH

Rare Daily Staff

The European Commission has extended the approval of Ultragenyx Pharmaceutical’s Evkeeza as an adjunct to diet and other lipid-lowering therapies to treat children aged 5 to 11 years with homozygous familial hypercholesterolemia.

Homozygous Familial Hypercholesterolemia (HoFH) is a devastating form of inherited hypercholesterolemia, affecting 1 in 300,000 people globally and approximately 1,600 people in the European Union. HoFH occurs when two copies of the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent, resulting in dangerously high levels of LDL-C, or bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events at an early age.

Evkeeza (evinacumab) 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 initially received EC decision as an adjunct to diet and other lipid-lowering therapies in adolescents and adults aged 12 years and older with HoFH in June 2021.

The EC decision follows the positive recommendation from the Committee for Medicinal Products for Human Use received in November 2023 and is based on the results of a phase 3 open-label study in patients ages 5-11 years with HoFH. 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 percent at week 24 on average. 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 was with the safety profile observed in adults and pediatric patients aged 12 years and older, with the additional adverse reaction of fatigue (reported in 3 patients).

“Evkeeza is a potentially life-changing therapy for the children and their parents affected by this rare and severe disorder,” said Magdalena Daccord, CEO of FH Europe Foundation. “As we advocate for childhood screening and detection to help improve early HoFH diagnosis, it is key to be able to offer to young patients appropriate and innovative treatment solutions along with lifestyle management.”

Evkeeza is delivered via 60-minute intravenous infusion once monthly (every 4 weeks). The treatment is now reimbursed and commercially available to prescribe for appropriate patients with HoFH in the U.S., Canada, Italy, and Germany. It is also available via early access schemes in Austria and France.

“It is critical to reduce LDL levels as early as possible for all people living with HoFH especially given that children as young as 5 years of age are at risk for severe cardiac events that can be life threatening,” said Eric Crombez, chief medical officer at Ultragenyx. “With its novel mechanism, Evkeeza combined with other lipid-lowering therapies has demonstrated the ability to significantly reduce LDL cholesterol levels beyond historical standard of care, which could have a transformational impact for these younger patients.”

Regeneron Pharmaceuticals discovered and developed Evkeeza, and commercializes the product in HoFH in the U.S. under the generic name evinacumab-dgnb, with dgnb as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Ultragenyx is responsible for commercialization efforts for Evkeeza in countries outside of the United States.

Photo: Eric Crombez, chief medical officer at Ultragenyx