Published March 28, 2016 This content is archived.
Richard W. Erbe, MD, professor of pediatrics and chief of the Division of Genetics, has co-authored a New England Journal of Medicine paper on a novel treatment for a rare genetic disorder that affects the body’s breakdown of cholesterol.
Erbe participated in conducting the Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) trial for patients with lysosomal acid lipase deficiency (LAL-D).
The life-threatening condition, which is caused by genetic mutations, makes the body accumulate cholesterol esters and triglycerides.
During the phase 3 trial, patients were infused with the enzyme replacement therapy sebelipase alfa, and they had meaningful improvements in multiple disease-related liver and lipid abnormalities.
In December 2015 — based on the trial’s results — sebelipase alfa, known by the brand name Kanuma, became the first therapy approved by the U.S. Food and Drug Administration for the treatment of LAL-D patients.
“This is the first safe and effective treatment to receive approval for this destructive disease,” says Erbe.
LAL-D leads to cholesteryl ester storage disease — an extremely rare condition that causes hyperlipidemia, enlarged liver, liver failure and dyslipidemia — and the more common Wolman disease, a condition that causes malnutrition and subsequent death during infancy.
In 2012, Erbe diagnosed a young boy with cholesteryl ester storage disease and was able to enroll him in the trial. “As fate would have it, at the time of diagnosis I was just learning that the ARISE study was being planned,” explains Erbe. “I moved quickly to position my patient for it.”
“He was the first newly diagnosed child with the disorder since the trial became available,” Erbe notes.
To test the efficacy of the enzyme replacement therapy, the study included a screening period; a 20-week double-blind, placebo-controlled period; and 16-week open-label period.
Overall, Erbe’s patient experienced positive results. He will receive infusions of the enzyme replacement therapy for the rest of his life, says Erbe.
Erbe and the study’s other collaborators recorded their patients’ data in a central repository, and their findings were reported in “A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency,” published in September 2015.
“Physicians have tended to be very aware of Wolman disease, the infantile form of LAL-D, but very unaware of cholesteryl ester storage disease,” says Erbe.
Awareness of the disease is so low that it is not uncommon for physicians to miss the diagnosis of cholesteryl ester storage disease in their patients, he explains. “In fact, my patient had seen a pediatrician and gastroenterologist before he came to me,” he says.
“It’s important we make the diagnosis where others have missed it and then provide meaningful treatment.”
Erbe leads an enzyme replacement therapy program that he established at Women and Children’s Hospital of Buffalo, and he trains pediatrics residents who he says “benefit greatly” from their work with enzyme therapy patients.
“Many of our patients are enthusiastic when they are finally diagnosed and are receiving treatment. Our trainees on rotation certainly have a very positive reaction to patients’ enthusiasm,” says Erbe. “More than that, residents have opportunities to learn about cholesteryl ester storage disease and many other conditions like it, which — although generally rare — are pretty common in our center.”
“Not all pediatrics residencies are able to provide their physicians with training in enzyme replacement therapy programs, but UB residents do get this experience,” says Erbe.
The multicenter study involved 66 patients. Erbe collaborated with physicians and researchers from institutions including:
Other collaborators are from hospitals and medical centers in countries including: