Sebelipase alfa (Kanuma®), a recombinant human enzyme-replacement therapy for lysosomal acid lipase deficiency (LAL-D), appears to be a safe treatment changing the natural history of the disease. This is according to Expert Opinion on Drug Safety.

Sebelipase alfa has been approved for the long-term treatment of early-onset and late-onset LAL-D patients by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) since 2015.

The drug safety evaluation was completed by Fatih Ezgü, a professor of pediatrics and head of the department of pediatric genetics at Gazi University, Faculty of Medicine in Ankara, Turkey.

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Ezgü conducted a literature review that included studies, case reports, and review articles about sebelipase alfa that were published through January 2021. In his evaluation, he focused on 6 clinical trials about the safety and efficacy of sebelipase alfa, and 2 case reports about the safety of the treatment.

“The documented adverse events related to sebelipase alfa almost always occurred as infusion reactions,” Ezgü wrote.

He added that most of these reactions were mild to moderate. They were easily managed using antihistamines, antipyretics, or steroids. In rare cases, anaphylaxis occurred. However, this could also be treated, and sebelipase alfa infusion resumed with desensitization without the need to stop the treatment.

People with LAL-D have a mutation in the LIPA gene, which causes the lysosomal acid lipase enzyme that it encodes not to function properly. This leads to the accumulation of triglycerides, cholesteryl esters, and other lipids inside the lysosomes causing damage.

Sebalipase alfa binds to cell surface receptors via the glycans that it expresses and is internalized into lysosomes where it hydrolyses cholesterase esters and triglycerides, transforming them into free cholesterol, glycerol, and fatty acids.


Ezgü F. Safety of sebelipase alfa for the treatment of lysosomal acid lipase deficiency. Expert Opin Drug Saf. Published online October 19, 2021. doi:10.1080/14740338.2022.1993186