Sebelipase alfa (Kanuma®, Kanuma™), the first commercially available recombinant human
lysosomal acid lipase (LAL), is approved in various countries worldwide, including those of the EU, the USA and Japan, as a long-term
enzyme replacement therapy for patients diagnosed with
LAL deficiency (LAL-D), an ultra-rare, autosomal recessive, progressive metabolic
liver disease. In an ongoing study in nine infants presenting with early-onset LAL-D (
Wolman disease), open-label treatment with
sebelipase alfa significantly improved 1-year survival compared with historical controls. A substantial mortality benefit was maintained at 2 years of age, as was a reduction in disease-related activity. In an ongoing study of 66 children and adults with late-onset LAL-D (
cholesteryl ester storage disease), 20 weeks' double-blind treatment with
sebelipase alfa significantly reduced multiple disease-related hepatic and
lipid abnormalities compared with placebo. Sustained improvements in markers of liver damage and dyslipidaemia were seen after 76 weeks' open-label treatment in an extension of this trial and, similarly, after 2 years' open-label treatment in an extension of another study in nine adults with late-onset LAL-D.
Sebelipase alfa therapy has thus far been generally well tolerated, with signs and symptoms consistent with
anaphylaxis being the most serious adverse reactions experienced by patients receiving the
drug in clinical trials. Due to the rarity of the disease, these studies have enrolled a limited number of patients. Nonetheless, the available data indicate that
sebelipase alfa is an effective disease-specific
therapy for individuals with LAL-D who have historically been managed using supportive
therapies (e.g.
cholesterol reduction,
hematopoietic stem cell transplantation, and
liver transplantation).