FDA approves first drug to treat a rare enzyme disorder in pediatric and adult patients

The U.S. Food and Drug Administration has approved Alexion’s Kanuma (sebelipase alfa) as the first treatment for patients with a rare disease known as lysosomal acid lipase (LAL) deficiency.

Kanuma is the first therapy approved in the U.S. for the treatment of patients with LAL-D, a genetic and progressive ultra-rare metabolic disease in which patients suffer multi-organ damage and premature death.

“We are pleased with the FDAapproval of Kanuma, a transformative treatment for patients with LAL-D, a devastating, ultra-rare disease that causes premature death in infants and multi-organ damage in those who survive,” saidDavid Hallal, Chief Executive Officer of Alexion.

“Importantly, the label includes a survival benefit in infants and reductions in important markers of liver disease, including ALT and liver fat content, as well as significant improvements in lipid parameters, in children and adults. This approval also strengthens Alexion’s global leadership in rare diseases as we broaden our product portfolio to transform the lives of more patients with severe and life-threatening disorders. We look forward to bringing Kanuma to patients with LAL-D and their physicians in the United States.”

“I am delighted that patients with LAL-D now have the first approved therapy that treats the underlying cause of the disease,” said Barbara K. Burton, M.D., lead clinical trial investigator, Professor of Pediatrics at the Northwestern University Feinberg School of Medicine and Attending Physician at the Ann and Robert H. Lurie Children’s Hospital of Chicago. “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. 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.”

Tuesday’s action involved approvals from two FDA centers. The Center for Veterinary Medicine (CVM) approved an application for a recombinant DNA (rDNA) construct in chickens that are genetically engineered (GE) to produce a recombinant form of human lysosomal acid lipase (rhLAL) protein in their egg whites. The FDA regulates GE animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act, because an rDNA construct introduced into an animal to change its structure or function meets the definition of a drug. The Center for Drug Evaluation and Research (CDER) approved the human therapeutic biologic (Kanuma), which is purified from those egg whites, based on its safety and efficacy in humans with LAL deficiency.

“LAL deficiency is a rare inherited genetic disorder that can lead to serious and life-threatening organ damage, especially when onset begins in infancy,” said CDER Director Janet Woodcock, M.D. “Using this technology, these patients for the first time ever have access to a treatment that may improve their lives and chances of survival.”

The new therapy, Kanuma, provides an rhLAL protein that functions in place of the missing, partially active or inactive LAL protein in the patient. Kanuma is produced by GE chickens containing an rDNA construct responsible for producing rhLAL protein in their egg whites. These egg whites are refined to extract the rhLAL protein that is eventually used to produce Kanuma and treat patients with LAL deficiency. The GE chickens are used only for producing the drug substance, and neither the chicken nor the eggs are allowed in the food supply.

Kanuma is approved for use in patients with LAL deficiency. Treatment is provided via intravenous infusion once weekly in patients with rapidly progressive LAL deficiency presenting in the first six months of life, and once every other week in all other patients.