FDA approves Kanuma (sebelipase alfa) for Lysosomal Acid Lipase Deficiency
FDA
The U.S. Food and Drug Administration approved Kanuma (sebelipase alfa) as the first treatment for patients with a rare disease known as lysosomal acid lipase (LAL) deficiency.
Patients with LAL deficiency (also known as Wolman disease and cholesteryl ester storage disease [CESD]) have no or little LAL enzyme activity. This results in a build-up of fats within the cells of various tissues that can lead to liver and cardiovascular disease and other complications.
Wolman disease often presents during infancy (around 2 to 4 months of age) and is a rapidly progressive disease. Patients with Wolman disease rarely survive beyond the first year of life. CESD is a milder, later-onset form of LAL deficiency and presents in early childhood or later. Life expectancy of patients with CESD depends on the severity of the disease and associated complications. Wolman disease affects one to two infants per million births, and CESD affects 25 individuals per million births.
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.
CDER evaluated the safety and efficacy of Kanuma in an open-label, historically controlled trial in nine infants with rapidly progressive Wolman disease and in a double-blind, placebo-controlled trial in 66 pediatric and adult patients with CESD.
In the trial in infants with Wolman disease, six of nine infants (67 percent) treated with Kanuma were alive at 12 months of age, whereas none of the 21 infants in the historical control group survived. In the trial in CESD patients, there was a statistically significant improvement in LDL-cholesterol levels and other disease-related parameters in those treated with Kanuma versus placebo after 20 weeks of treatment.
The most common side effects observed in patients treated with Kanuma are diarrhoea, vomiting, fever, rhinitis, anemia, cough, headache, constipation, and nausea. Kanuma is produced by Alexion Pharmaceuticals Inc., based in Cheshire, Connecticut.
Source: FDA
