FDA approves enzyme replacement therapy for metabolic disorder

The FDA announced its approval of Kanuma, an enzyme replacement therapy, for the treatment of adult and pediatric patients diagnosed with lysosomal acid lipase deficiency.

Kanuma (sebelipase alfa, Alexion Pharmaceuticals, Inc.) is the first therapy approved in the U.S. for the treatment of patients with lysosomal acid lipase deficiency (LAL-D), a rare metabolic disease in which patients have little or no LAL enzyme activity. This absence results in a build-up of fats within the cells of various tissues that can lead to liver and cardiovascular disease and other complications, according to the FDA.

“LAL deficiency is a rare inherited genetic disorder that can lead to serious and life-threatening organ damage, especially when onset begins in infancy,” Janet Woodcock, MD, Center for Drug Evaluation and Research director at the FDA, said in a press release. “Using this technology, these patients for the first time ever have access to a treatment that may improve their lives and chances of survival.”

LAL deficiency, also known as Wolman disease, affects one to two infants per 1 million births, and cholesteryl ester storage disease (CESD) affects 25 people per 1 million births, according to the FDA. Wolman Disease most commonly begins around 2 to 4 months of age, and those diagnosed rarely survive beyond 1 year. The FDA labels CESD as a “later-onset form of LAL deficiency” and can begin later on in life. Life expectancy of patients with CESD depends on the severity of the disease and associated complications.

“In the absence of treatment, LAL-D is nearly always fatal in infants and puts pediatric and adult patients at high risk of vital organ damage and premature mortality,” Barbara K. Burton, MD, professor of pediatrics, Northwestern University Feinberg School of Medicine, and attending physician, Ann and Robert H. Lurie Children’s Hospital of Chicago, said in a press release. “In clinical studies, 67% of infants who received enzyme replacement therapy survived beyond 12 months of age, and children and adults had meaningful improvements in multiple disease-related liver and lipid abnormalities.”

Barbara K. Burton

In a previous study conducted by Burton and colleagues, they found that sebelipase alfa reduced hepatic and lipid abnormalities among adults and children with LAL-D.

“This study is important because it demonstrates that sebelipase alfa can reduce fat accumulation in the liver in patients with LAL-D with subsequent improvement or normalization of alanine aminotransferase,” Burton previously told Healio.com/Hepatology. “This should improve the outcome of this disorder which, untreated, leads to cirrhosis and liver transplantation.”

Sebelipase alfa can be administered via intravenous infusion once weekly in patients with rapidly progressive LAL deficiency presenting in the first 6 months of life, and once every other week in all other patients, according to the FDA

The drug will be commercially available in January 2016, according to the Alexion website.

Disclosure: Woodcock is employed by the FDA. Burton reports receiving consulting fees from BioMarin Pharmaceutical, Shire, REGENXBIO and Hyperion Therapeutics; lecture fees from Genzyme and Shire; and grant support from Genzyme, BioMarin Pharmaceutical, Shire, Synageva BioPharma, Ultragenyx Pharmaceutical and Cytonet.