Regulatory Decision Summary for Kanuma

Kanuma (sebelipase alfa) is a recombinant form of human lysosomal acid lipase (rhLAL) developed as an enzyme replacement therapy for lysosomal acid lipase deficiency (LALD). LALD is a rare, autosomal recessive genetic disorder in which LAL enzyme activity is significantly reduced. This leads to the accumulation of cholesteryl esters and triglycerides in multiple organs, and complications in and from these organs (e.g. liver fibrosis/cirrhosis, dyslipidemia).

LALD occurs in all ages and is most severe in infants. LALD in children and adults is a milder form of LALD whereby life expectancy varies depending on the severity of the disease and associated complications.

Children and adults with LALD were treated with Kanuma or placebo in Study LAL-CL02. The results showed a significantly greater improvement in lipid parameters including low-density lipoprotein cholesterol (LDL-c) at the completion of the 20-week double-blind period of the study in subjects treated with Kanuma compared to subjects treated with placebo. A reduction in LDL-c likely represents a clinical benefit in this patient population since LALD patients exhibit dyslipidemia and are at risk for atherosclerosis. Therefore, even though the effects of the observed improvements in lipid parameters on cardiovascular morbidity and mortality have yet to be established, the efficacy results are considered promising.

An improvement in liver chemistry was also observed in Kanuma-treated patients. However, it is unclear how this improvement relates to liver disease progression in patients with LALD.

LALD in infants is also known as Wolman disease and is a rapidly progressive disease, especially if the affected infants present with early growth failure (before 6 months of age). These infants rarely survive beyond the first year of life. LALD infants were treated with Kanuma in Study LAL-CL03. The results showed that 6 out of 9 Kanuma -treated infants with rapidly progressive LALD and growth failure within the first 6 months of age survived to 12 months, compared to 0 of 21 infants in the historical cohort from an observational study.

The safety profile of Kanuma was found to be acceptable and consistent with other enzyme replacement therapies.

There is currently no market authorized therapy for patients with LALD in Canada.

In view of the promising survival outcome in infants with LALD which is considered rare and life-threatening, the improvements in lipid parameters observed in children and adults, and the manageable safety profile of Kanuma, the overall risk/benefit profile of Kanuma is considered favourable. As such, Kanuma meets the NOC/c criteria of promising clinical benefit, for patients with LALD.

A Risk Management Plan has also been required by Health Canada in order to ensure that the promising benefits of Kanuma continue to outweigh the risks in the longer term.

For more information on Health Canadas decision, please view the Summary Basis of Decision.