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Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.

ABSTRACT: Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain. No patient developed anti-drug antibodies and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Statistically significant reductions in liver (31%) and spleen (39%) volumes were maintained through 30 months of treatment. There was a mean increase in lung diffusing capacity of 35%, and clinically relevant improvements in infiltrative lung disease parameters. Lipid profiles improved in all patients. Improvements in bone mineral density of the spine were observed in some patients. Chitotriosidase in serum and lyso-sphingomyelin in dried blood spots decreased with olipudase alfa treatment, suggesting utility as biomarkers for monitoring treatment efficacy. Olipudase alfa is the first etiology-specific treatment in development for ASMD. This study demonstrates that treatment with olipudase alfa for 30 months is well-tolerated and associated with life-transforming sustained improvements in relevant disease clinical measures.

SUBMITTER: Wasserstein MP

PROVIDER: S-EPMC6133173 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.

Wasserstein Melissa P MP Diaz George A GA Lachmann Robin H RH Jouvin Marie-Hélène MH Nandy Indrani I Ji Allena J AJ Puga Ana Cristina AC

Journal of inherited metabolic disease 20180105 5

Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mil ...[more]

PMID: 29305734

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Project description:Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration, leading to death typically by the age of 3 years, most often from respiratory failure. In contrast, the clinical phenotype and life expectancy of patients with NPD B may vary widely. Almost all patients have hepatosplenomegaly and an atherogenic lipid profile, and most patients have interstitial lung disease with progressive impairment of pulmonary function and hematologic abnormalities including cytopenias. Other common clinical manifestations include liver dysfunction, heart disease, skeletal abnormalities and growth delays. Some patients with ASMD who survive beyond early childhood have intermediate phenotypes (variant NPD B) characterized by combinations of non-neurologic and mild to severe neurologic symptoms. The physical and psychosocial burden of illness in patients with NPD B is substantial. Common symptoms include shortness of breath, joint or limb pain, abdominal pain, bleeding and bruising. The disease often leads to chronic fatigue, limited physical or social activity and difficulties in performing daily activities or work. Many patients die before or in early adulthood, often from pneumonia/respiratory failure or liver failure. Available treatments are limited to symptom management and supportive care. An enzyme replacement therapy currently in clinical development is expected to be the first treatment addressing the underlying pathology of the disease. Early diagnosis and appropriate management are essential for reducing the risk of complications. While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.

Dataset Information

Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.

Publications

Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.

Similar Datasets

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