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FDA Approves First Treatment for Rare Enzyme Disorder

Sebelipase provides missing protein in lysosomal acid lipase deficiency

The FDA has given the nod to sebelipase alfa (Kanuma, Alexion Pharmaceuticals) as the first treatment for patients with lysosomal acid lipase (LAL) deficiency, a rare disease.

Patients with LAL deficiency –– also known as Wolman disease and cholesteryl ester storage disease (CESD) –– have no or little LAL enzyme activity. This results in a build-up of fats within the cells of various tissues, which can lead to liver and cardiovascular disease and other complications. Wolman disease often presents during infancy (around 2 to 4 months of age) and is a rapidly progressive disease. Patients with Wolman disease rarely survive beyond the first year of life. CESD is a milder, later-onset form of LAL deficiency and presents in early childhood or later. The life expectancy of patients with CESD depends on the severity of the disease and on associated complications. Wolman disease affects one to two infants per million births, and CESD affects 25 individuals per million births.

The FDA’s Center for Drug Evaluation and Research (CDER) approved sebelipase alfa based on its safety and efficacy in human subjects with LAL deficiency. The new therapy provides an rhLAL protein that functions in place of the missing, partially active, or inactive LAL protein in the patient. Sebelipase is produced by chickens containing an rDNA construct responsible for producing rhLAL protein in their egg whites. These egg whites are refined to extract the rhLAL protein that is eventually used to produce sebelipase and treat patients with LAL deficiency.

Sebelipase is approved for use in patients with LAL deficiency. Treatment is provided via intravenous infusion once weekly in patients with rapidly progressive LAL deficiency presenting in the first 6 months of life, and once every other week in all other patients.

The CDER evaluated the safety and efficacy of sebelipase in an open-label, historically controlled trial in nine infants with rapidly progressive Wolman disease and in a double-blind, placebo-controlled trial in 66 pediatric and adult patients with CESD. In the study in infants with Wolman disease, six of the nine infants (67%) treated with sebelipase were alive at 12 months of age, whereas none of the 21 infants in the historical control group survived. In the trial in CESD patients, there was a statistically significant improvement in low-density lipoprotein cholesterol levels and other disease-related parameters in those treated with sebelipase compared with placebo after 20 weeks of treatment.

The most common adverse effects observed in patients treated with sebelipase alfa included diarrhea, vomiting, fever, rhinitis, anemia, cough, headache, constipation, and nausea.

Source: FDA; December 8, 2015.

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