NOVATO, Calif. — Ultragenyx Pharmaceutical Inc. today announced that the European Commission (EC) has extended the approval of Evkeeza® (evinacumab) as an adjunct to diet and other lipid-lowering therapies to treat children aged 5 to 11 years 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 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.
“This approval heralds a new era for treatment of children 5 to 11 years of age with HoFH,” stated Albert Wiegman, M.D., Ph.D. and Professor, Department of Paediatrics at Amsterdam University Medical Center. “The addition of Evkeeza to aggressive baseline lipid-lowering therapy nearly halves LDL-C levels in a disorder with an extremely high risk of premature cardiovascular disease in young patients, where achieving LDL-C goals otherwise isn’t possible.
This 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.1 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 paediatric patients with HoFH. With the addition of Evkeeza, children (n=14) were able to reduce their LDL-C by 48% 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 waswith the safety profile observed in adults and paediatric patients aged 12 years and older, with the additional adverse reaction of fatigue (reported in 3 patients).
“It is with immense joy that the international community of parents and caregivers of children with HoFH welcomes this approval, because Evkeeza is a potentially life-changing therapy for the children and their parents affected by this rare and severe disorder,” stated Magdalena Daccord, chief executive officer 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. That said, it will be a true success once this therapy option is available to all those who need it as soon as they need it to support their treatment goals.”
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,”2 said Eric Crombez, M.D., 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.”
About the Pivotal Paediatric Trial
The three-part, single-arm, open-label trial evaluated Evkeeza added to other lipid-lowering therapies in paediatric patients with HoFH aged 5 to 11 years. Part A (n=6) was a Phase 1b trial designed to assess the pharmacokinetics (PK), safety and tolerability of Evkeeza. Part B (n=14) evaluated the efficacy of Evkeeza during a 24-week treatment period and enrolled patients with an average age of 9 years. Among them, 86% were on statins, 93% were on ezetimibe, 50% were on LDL apheresis and 14% were on lomitapide. Patients received Evkeeza 15 mg/kg every four weeks delivered intravenously in addition to their baseline lipid-lowering treatment regimen. The primary endpoint was change in LDL-C at week 24. Secondary endpoints included the effect of Evkeeza on other lipid parameters (i.e., apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein[a] and total cholesterol), efficacy by mutation status, safety and tolerability, immunogenicity and PK. Patients who completed Part A or B were allowed to, and all did, continue treatment in Part C (n=20), a completed Phase 3 extension trial. This trial was not designed to evaluate the effect of Evkeeza on cardiovascular events.
Evkeeza was well tolerated in this patient population. 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.
About Homozygous Familial Hypercholesterolemia (HoFH)
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 (>400 mg/dL) of LDL-C, or bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events at an early age.
About Evkeeza® (evinacumab)
Evinacumab, the active substance in Evkeeza, attaches to a protein in the body called ANGPTL3 and blocks its effects. ANGPTL3 is involved in controlling cholesterol levels and blocking its effect reduces the level of cholesterol in the blood. Evkeeza is delivered via an infusion every month (4 weeks).
Evkeeza is approved by the European Commission (EC) as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C) lowering therapies for the treatment of paediatric patients aged 5 years and older with homozygous familial hypercholesterolemia (HoFH). The effects of Evkeeza on cardiovascular morbidity and mortality have not been determined. Regeneron Pharmaceuticals, Inc. 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 U.S.
Contact
Jeff Blake
415-612-7784
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