Evkeeza phase III trial demonstrates 48% LDL-C reduction in children with ultra-rare form of high cholesterol.-Regeneron.

The trial met its primary endpoint, showing children who added investigational Evkeeza to other lipid-lowering therapies reduced their low-density lipoprotein-cholesterol (LDL-C) by 48% at week 24 on average. Detailed results were presented at the 5th European Atherosclerosis Society Pediatric Familial Hypercholesterolemia symposium and will form the basis of a regulatory submission to the FDA later this year.

"Children living with HoFH have an incredibly rare and severe disease that causes dangerously high LDL-C levels. On current treatment options alone, many patients don't reach their treatment goals, leaving them with an uncertain future," said M. Doortje Reijman, M.D., Research Associate in Pediatric Metabolic Diseases and Nephrology at the Amsterdam University Medical Center, and a trial investigator. "Evinacumab has already demonstrated significant LDL-C reductions in adolescents and adults with HoFH. This latest Phase III trial illustrates the potential of this medicine to be a breakthrough HoFH therapy for children as young as 5-years old, helping them control their LDL-C early in the course of their disease."

Despite treatment with other lipid-lowering therapies, children (n=14) entered the trial with an average LDL-C level of 264 mg/dL, more than twice the target (<130 mg dl) for pediatric patients with hofh. after 24 weeks of evkeeza treatment (15 mg kg every 4 weeks delivered intravenously [iv]), the phase iii trial met its primary endpoint with additional results showing: i.79% of patients reduced their ldl-c by at least half. ii. an absolute 132 mg dl reduction in ldl-c from baseline, on average. iii. reductions in levels of all lipid endpoint parameters assessed, which were generally observed within the first 8 weeks of treatment. these lipid parameters were apolipoprotein b, non-high-density lipoprotein cholesterol, lipoprotein(a) and total cholesterol.></130>

Evkeeza was generally well-tolerated with all patients completing the trial. The most common adverse events (AEs) were throat pain (oropharyngeal pain, 21%) as well as upper abdominal pain, diarrhea, headache and nasopharyngitis (all 14%). There were 2 severe AEs (aortic stenosis and tonsilitis), both of which were considered unrelated to treatment.

Evkeeza is the first ANGPTL3-targeted (angiopoietin-like 3-targeted) therapy approved by the FDA (as evinacumab-dgnb) and European Commission as an adjunct therapy for certain patients aged 12 years and older with HoFH. The potential use of Evkeeza in HoFH patients aged 5 to 11 years is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.