Rare Disease Report: FDA Approves Alexion’s Kanuma for LAL Deficiency

January 7, 2016

The FDA approved Alexion’s Kanuma (sebelipase alfa) to treat patients with lysosomal acid lipase (LAL) deficiency. Kanuma is an enzyme replacement therapy.

What is LAL Deficiency?

Lysosomal acid lipase deficiency, also known as Wolman disease and cholesteryl ester storage disease (CESD), is a rare autosomal recessive lysosomal storage disease where the body does not produce enough active lysosomal acid lipase (LAL or LIPA) enzyme. Synptoms include vomiting, diarrhea, abdominal distention, weightless and hepatosplenomegaly.

Today’s action involved approvals from 2 FDA centers. The Center for Veterinary Medicine (CVM) approved an application for a recombinant DNA (rDNA) construct in chickens that are genetically engineered to produce a recombinant form of human lysosomal acid lipase (rhLAL) protein in their egg whites. The Center for Drug Evaluation and Research then approved Kanuma use in patients with LAL deficiency. Kanuma provides an rhLAL protein that functions in place of the missing LAL protein in the patient.


The approval stems from an open label controlled trial of 9 infants with Wolman Disease and also a double-blind, placebo-controlled trial in 66 pediatric and adult patients with CESD. In the trial in infants with Wolman disease, 6 of 9 infants (67 percent) treated with Kanuma were alive at 12 months of age, while 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 diarrhea, vomiting, fever, rhinitis, anemia, cough, headache, constipation, and nausea.

CVM Approval

In its review of the genetically engineered chicken application, CVM assessed the safety of the rDNA construct, including the safety of the rDNA construct to the animals, as well as a full review of the construct and its stability in the genome of the chicken. No adverse outcomes were noted in the chickens. As required by the National Environmental Policy Act and its implementing regulations, CVM evaluated the potential environmental impacts of approval of the sponsor’s genetically engineered chickens and determined that the approval does not cause any significant impact on the environment, because the chickens are raised in highly secure indoor facilities.

“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 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.”

Kanuma was developed by by Synageva, a company that was bought by Alexion on June 23, 2015. The FDA then extended Kanuma’s PDUFA date to review manufacturing data.


FDA approves first drug to treat a rare enzyme disorder in pediatric and adult patients [news release]. US Food and Drug Association: December 8, 2015.


Thanks to Rare Disease Report for this piece. 

Stay Connected

Sign up for updates straight to your inbox.