The U.S. Food and Drug Administration (FDA) has approved olipudase alfa for intravenous infusion in pediatric and adult patients with Acid Sphingomyelinase Deficiency (ASMD).

ASMD is an autosomal recessive genetic disorder caused by mutations in the SMPD1 gene. That gene encodes for acid sphingomyelinase (ASM), an enzyme that metabolizes sphingomyelin. ASMD is also knows as Niemann-Pick disease types A, A/B, and B. Olipudasae alfa is an enzyme replacement therapy designed to replace the deficient or defective ASM.

In the more severe, infantile form of ASMD, both central and peripheral symptoms are present while in the less severe adult forms, largely peripheral symptoms dominate.

Infantile ASMD has an onset in early infancy and is marked by progressive and eventually massive hepatosplenomegaly, progressive neurological symptoms, pulmonary damage, and cholesterol abnormalities. Other symptoms include respiratory and gastrointestinal, cherry red maculae, feeding problems, failure to thrive, and irritability.

Chronic visceral ASMD has a variable age of onset from infancy to adulthood. Patients with chronic visceral ASMD show similar morbidities of hepatosplenomegaly, progressive pulmonary dysfunction, thrombocytopenia, and dyslipidemia. These patients may develop clinically significant skeletal disease, cardiac valve abnormalities, stunted growth, and delayed puberty associated with the advancement of disease in the various organ systems.

In between these two extremes, patients with chronic neurovisceral ASMD present with similar symptoms as the chronic visceral form of the disease but may also develop neurologic symptoms of gross motor delay, ataxia and learning disability.

The approval was largely based on a randomized, double-blind, placebo-controlled study of 31 patients given olipudase alfa or placebo. In the trial, the orphan drug was shown to improve lung function and reduced liver and spleen size.

The most common side effects include headache, cough, fever, joint pain, diarrhea, and low blood pressure. The drug carries a boxed warning for severe hypersensitivity reactions including anaphylaxis.

The FDA awarded the sponsor (Sanofi)  a rare pediatric disease priority review voucher since it has an indication for children. The voucher can be used by Sanofi to any drug they submit to the FDA and receive a priority review (i.e., the FDA will review the application within 6 months instead of the standard 10 months). The voucher can also be sold to other companies and the price tag can be in excess of $90 million.

The news of the approval was heralded by the Niemann-Pick community. In an exclusive interview with CheckRare, Joslyn Crowe, executive director of the National Niemann-Pick Disease Foundation (NNPDF) talks about the approval and its impact on families caring for people with ASMD.



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