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

Melissa P. Wasserstein, George A. Diaz, Robin H. Lachmann, Marie Hélène Jouvin, Indrani Nandy, Allena J. Ji, Ana Cristina Puga

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Inherited Metabolic Disease
DOIs
StateAccepted/In press - Jan 5 2018

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Type A Niemann-Pick Disease
Safety
Acids
Therapeutics
Enzyme Replacement Therapy
Lung Volume Measurements
Sphingomyelin Phosphodiesterase
Sphingomyelins
Vital Signs
Hematology
olipudase alfa
Bone Density
Nausea
Abdominal Pain
Lung Diseases
Headache
Anti-Idiotypic Antibodies
Spine
Spleen
Biomarkers

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD) : safety and efficacy in adults treated for 30 months. / Wasserstein, Melissa P.; Diaz, George A.; Lachmann, Robin H.; Jouvin, Marie Hélène; Nandy, Indrani; Ji, Allena J.; Puga, Ana Cristina.

In: Journal of Inherited Metabolic Disease, 05.01.2018, p. 1-10.

Research output: Contribution to journalArticle

Wasserstein, Melissa P. ; Diaz, George A. ; Lachmann, Robin H. ; Jouvin, Marie Hélène ; Nandy, Indrani ; Ji, Allena J. ; Puga, Ana Cristina. / Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD) : safety and efficacy in adults treated for 30 months. In: Journal of Inherited Metabolic Disease. 2018 ; pp. 1-10.
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