FDA OKs First Drug (Kanuma) for Rare Enzyme Disease

December 08, 2015

The US Food and Drug Administration (FDA) today approved sebelipase alfa (Kanuma, Alexion Pharmaceuticals), the first treatment for a rare genetic condition called lysosomal acid lipase (LAL) deficiency, with chickens sharing some of the credit.

The new drug is a recombinant form of the human LAL enzyme produced in the egg whites of genetically engineered chickens. This recombinant human LAL makes up for the missing, partially active, or inactive LAL in humans with the deficiency, according to an FDA news release.

Left untreated, LAL deficiency causes cholesterol esters and triglycerides to build up in vital organs such as the liver, which can lead to liver and cardiovascular disease and other complications. A rapidly progressive form of the condition called Wolman disease often presents in infants at 2 to 4 months of age. These infants rarely survive beyond a year. Cholesteryl ester storage disease (CESD) is a milder version of LAL deficiency that presents later in childhood and beyond. With CESD, life expectancy depends on disease severity.

The genetically modified chickens that contribute the crucial replacement enzyme are not allowed in the nation's food supply, and neither are the eggs.

"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 Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research (CDER). "Using this technology, these patients for the first time ever have access to a treatment that may improve their lives and chances of survival."

Two separate FDA offices signed off on the new drug. The agency's Center for Veterinary Medicine approved the recombinant DNA construct in the genetically engineered chickens that codes for the replacement enzyme. CDER, in turn, approved the human biologic product, purified from egg whites.

CDER determined that sebelipase alfa was safe and effective on the basis of two trials. The first was an open-label, historically controlled trial in nine infants with Wolman disease who were treated with the drug. Six of the nine infants were alive at 12 months of age. In contrast, none of the 21 infants in the historical control group lived that long.

The second trial, double-blinded and placebo-controlled, involved 66 pediatric and adult patients with CESD. After 20 weeks of therapy, patients treated with sebelipase alfa posted statistically significant improvements in low-density lipoprotein cholesterol levels and other disease-related metrics compared with patients receiving the placebo.

For its part, the Center for Veterinary Medicine assessed both the safety of the recombinant DNA construct in chickens and its stability in the animal's genome over several generations. No adverse events were observed. The Center for Veterinary Medicine also determined that approving the genetically engineered chickens for medicinal purposes "does not cause any significant impact on the environment, because the chickens are raised in highly secure indoor facilities," the FDA said.

The most common adverse effects observed in patients treated with sebelipase alfa are diarrhea, vomiting, fever, rhinitis, anemia, cough, headache, constipation, and nausea.

More information about today's announcement is available on the FDA website.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.