Evolocumab Drops Pediatric Familial Hypercholesterolemia LDL-C by 44%


The new findings break ground on placebo-controlled assessment of the PCSK9 inhibitor for the pediatric population.

Evolocumab (Repatha) significantly improved low-density lipoprotein cholesterol (LDL-C) levels in pediatric patients with familial hypercholesterolemia, according to a new study.

The phase 3 findings, presented during a late-breaking session at the European Society of Cardiology (ESC) 2020 Congress this weekend, give clinicians incentive to further understand the benefit of the PCSK9 inhibitor drug class among children suffering from the most common monogenic disorder in the world.

The HAUSER-RCT Investigators, led by Daniel Gaudet, MD, PhD, a lipidologist and professor of Medicine at the University of Montreal, cited growing evidence suggesting pathophysiological atherosclerotic changes among patients with familial hypercholesterolemia begin early into life—suggesting the need for early reduction and management of LDL-C levels.

“Despite appropriate treatment, guideline-recommended LDL cholesterol levels are not achieved in some patients with familial hypercholesterolemia,” Gaudet and colleagues wrote.

The team assessed evolocumab, a fully human monoclonal antibody which prevents PCSK9 from harming the LDL receptor and has been shown to reduce LDL-C levels in adults by up to 60%. Its initial approval by the US Food and Drug Administration (FDA) in 2015 was for the treatment LDL-C levels in adults with hyperlipidemia, including familial hypercholesterolemia.

The 24-week, randomized, double-blind, placebo-controlled HAUSER trial gauged the efficacy and safety of evolocumab in pediatric patients aged 10-17 years old with heterozygous familial hypercholesterolemia.

Their patient population had been on stable lipid-lowering therapy for at least 4 weeks prior to screening, and with LDL-C levels ≥130 mg/dL, as well as triglyceride levels of ≤400 mg/dL.

The 157 eligible patients were randomly assigned 2:1 to either monthly subcutaneous injections of 420mg evolocumab or placebo. Gaudet and colleagues assessed for a primary endpoint of percent change in LDL-C from baseline to week 24.

Key secondary endpoints included mean percent change in LDL-C from baseline to weeks 22-24, and the absolute change in patient LDL-C level from baseline to week 24.

Mean patient age for evolocumab (n = 104) and placebo (n = 53) treatment arms were approximately 13.7 years old, with even disparities in patients <14 years old and ≥14 years old. A majority of patients (100 [63.7%]) were female; 84.7% were white.

At 24 weeks, mean percent change from baseline in LDL-C was -44.5% among evolocumab patients, and -6.2% among placebo patients—a significant absolute difference of 38.3 percentage points (P <.001).

Evolocumab-treated patients improved absolute change in LDL-C by 68.6 mg/dL versus placebo (-77.5 vs -9.0; P <.001).

Across secondary endpoints for lipid variables, evolocumab bettered placebo. Investigators observed a similar rate of adverse events across both treatment groups.

In an interview with HCPLive® regarding the HAUSER findings, Gaudet emphasized the new ground his team has not only treaded, but found success on: evolocumab has never been assessed versus a placebo control in a pediatric population.

“An important element to highlight: we were expecting such results, but since it’s never been evaluated, it might be of important interest to those young FH patients not being a target and being at very high risk due to their family history of cardiovascular disease,” he said.

Gaudet emphasized breaking ground on pediatric PCSK9 inhibitor use for familial hypercholesterolemia is a natural, but important step. It’s not done yet, though.

“What we need is to assess the safety and efficacy over time,” Gaudet said. “That is a critical element in the pediatric population in particular.”

He and colleagues are seeking indication evolocumab that is a long-term solution for the widely burdensome, genetic-driven cardiovascular disease. Initial findings look promising.

“We found that monthly evolocumab provided substantial LDL cholesterol lowering at 24 weeks when added to background lipid-lowering therapy in pediatric patients with heterozygous familial hypercholesterolemia,” investigators concluded.

The study, “Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia,” was published online in The New England Journal of Medicine.

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