The most common LIPA gene mutation, found in about half of individuals with LAL deficiency that begins in childhood or later, is called a splice-site mutation where there is a substitution of guanine for adenine near an area of the gene called exon 8 (IVS8-1G>A).
Early-onset LAL deficiency, also known as Wolman disease, typically presents within the first weeks of life, and affected infants usually die within six to twelve months. The common symptoms for the disease in infants are prominent hepatosplenomegaly, diarrhea and vomiting, malabsorption, growth failure, and liver failure. Late-onset LAL deficiency, also known as cholesteryl ester storage disease, has a mean age of onset of five years with the primary symptom of hepatomegaly.
Sebelipase alfa (KanumaŽ) was approved by the FDA on December 8, 2015 for the treatment of individuals with a diagnosis of lysosomal acid lipase deficiency. Sebelipase alfa (KanumaŽ) is a recombinant human lysosomal acid lipase catalyzing the hydrolysis of cholesteryl ester to free cholesterol and free fatty acids.
A multicenter, open-label, single-arm clinical study on the efficacy of sebelipase alfa (KanumaŽ) was conducted in nine infants with LAL deficiency who had growth failure or other rapidly progressive disease prior to six months of age. Efficacy was assessed by comparing the survival of infants treated with sebelipase alfa (KanumaŽ) to 21 historical cohort infants with a similar age at disease presentation and clinical characteristics who were not treated with sebelipase alfa (KanumaŽ). Of the nine infants on sebelipase alfa (KanumaŽ), six survived beyond 12 months of age compared to the historical cohort infants with zero surviving past 12 months, all of whom died by eight months of age. The median age of the six infants who survived beyond 12 months was 18.1 months.
The safety and efficacy of sebelipase alfa (KanumaŽ) were assessed in 66 pediatric and adult individuals with late-onset LAL deficiency, age range 4 to 58 years, in a multicenter, double-blind, placebo-controlled trial. At the completion of the 20-week double-blind period, the sebelipase alfa (KanumaŽ)-treated group had a statistically significant improvement in percent change from baseline in LDL-c, non-HDL-c, triglycerides, and HDL-c than the placebo group. Individuals treated with sebelipase alfa (KanumaŽ) had a larger reduction from baseline in ALT values and liver fat content compared to individuals treated with placebos.
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
Policy: MA00.024b:Reporting Requirements for Drugs and Biologics
Policy: MA08.012c:Off-label Coverage for Prescription Drugs and/or Biologics