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).
