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Evkeeza® (evinacumab) Phase 3 Trial Demonstrates 48% LDL-C Reduction in Children with Ultra-rare Form of High Cholesterol

TARRYTOWN, N.Y., May 21, 2022 – Children already on other lipid-lowering therapies entered the trial with dangerously high LDL-C (264 mg/dL on average), and 79% saw their LDL-C reduced by at least half at 24 weeks

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive results from a Phase 3 trial evaluating Evkeeza® (evinacumab) in children aged 5 to 11 with homozygous familial hypercholesterolemia (HoFH). 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 today at the 5th European Atherosclerosis Society Pediatric Familial Hypercholesterolemia symposium and will form the basis of a regulatory submission to the U.S. Food and Drug Administration (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 3 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 3 trial met its primary endpoint with additional results showing:

79% of patients reduced their LDL-C by at least halfAn absolute 132 mg/dL reduction in LDL-C from baseline, on averageReductions 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.

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.

About HoFH
HoFH is an ultra-rare inherited condition, and the most severe form of familial hypercholesterolemia (FH). The disease affects 1 in 160,000 to 300,000 people worldwide and approximately 1,300 in the U.S. HoFH occurs when two copies of the FH-causing genes are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of LDL-C, or bad cholesterol. Those living with HoFH are at risk for premature atherosclerotic disease and life-threatening cardiac events as early as their teen years.

About the trial
The Phase 3 data are the Part B portion of a three-part, single-arm, open-label trial evaluating Evkeeza in pediatric patients with HoFH aged 5 to 11 years. In Part B, 14 patients were enrolled 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.

During the 24-week treatment period, patients received Evkeeza 15 mg/kg every four weeks via IV alongside their 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, efficacy by mutation status, safety and tolerability, immunogenicity and pharmacokinetics (PK).
Part A was a Phase 1b trial designed to assess the PK, safety and tolerability of Evkeeza. Patients who completed Part A or B were allowed to continue treatment in Part C, an ongoing Phase 3 extension trial. Parts A, B and C were not designed to evaluate the effect of Evkeeza on cardiovascular events.
About Evkeeza® (evinacumab)
Evkeeza was invented using Regeneron’s VelocImmune® technology and is a fully human monoclonal antibody that binds to and blocks the function of ANGPTL3, a protein that inhibits lipoprotein lipase (LPL) and endothelial lipase (EL) and regulates circulating lipids, including LDL-C.
Regeneron scientists discovered the angiopoietin gene family more than two decades ago (see publications from 1996, 1997 and 1999). Human genetics research published in New England Journal of Medicine in 2017 by scientists from the Regeneron Genetics Center® found that patients whose ANGPTL3 gene did not function properly (called a “loss-of function mutation”) have significantly lower levels of key blood lipids, including LDL-C, and that this is associated with a significantly lower risk of coronary artery disease.
The generic name for Evkeeza in its approved U.S. indications is evinacumab-dgnb, with dgnb the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. 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.
Regeneron is responsible for the development and distribution of Evkeeza in the U.S. and is collaborating with Ultragenyx to clinically develop, commercialize and distribute Evkeeza outside of the U.S.
About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately one in five of all original, FDA-approved fully human monoclonal antibodies currently available. This includes Evkeeza® (evinacumab-dgnb), REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
This article was shared with Prittle Prattle News as a Press Release.
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