Olipudase alfa for acid sphingomyelinase deficiency: Evidence of efficacy from a compassionate use program
11 affiliations
- 1Division of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy
- 2Metabolic Diseases Unit, Department of Pediatrics, Buzzi Children's Hospital, Milan, Italy
- 3Unit of Internal Metabolic Medicine, University of Modena and Reggio Emilia, Baggiovara University Hospital AOU of Modena, Modena, Italy
- 4Department of Clinical Medicine and Surgery University of Naples "Federico II", Naples, Italy
- 5Metabolic Diseases Unit Santobono-Pausilipon Children's Hospital, Naples, Italy
- 6Department of Translational Medical Sciences, Federico II University, Naples, Italy
- 7Unit of Expanded Neonatal Screening and Inherited Metabolic Diseases, Pediatric Clinic, Department of Medical Sciences, University of Catania, Catania, Italy
- 8Dipartimento di Scienze Cliniche e di Comunità, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan, Italy
- 9SC Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- 10Regional Coordinating Centre for Rare Diseases, University Hospital of Udine, Udine, Italy
- 11Department of Medicine and Surgery, University of Bologna, Bologna, Italy.
Abstract
Background: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by mutations in the SMPD1 gene, leading to systemic accumulation of sphingomyelin, primarily affecting the liver, spleen, lungs, and central nervous system (CNS). Olipudase alfa represents the first approved enzyme replacement therapy (ERT) targeting the non-neurological manifestations of ASMD. This study evaluates real-world safety and efficacy data of olipudase alfa in a cohort of Italian patients.
Methods: We retrospectively analyzed clinical, radiological, and laboratory data from 8 Italian patients (5 pediatric, 3 adult) with chronic visceral or chronic neurovisceral ASMD. All patients received olipudase alfa through a compassionate use program between December 2021 and November 2023. Data was collected at baseline, 3, 6, 9, 12, and 15 months of treatment.
Results: At baseline, the cohort exhibited hepatosplenomegaly, interstitial lung disease, dyslipidemia, cytopenias, and hypertransaminasemia. Treatment led to significant improvements in hematological parameters, lipid profiles, and liver enzymes. A marked reduction in lyso-sphingomyelin levels was observed, alongside a decrease in spleen and liver volumes. Pulmonary function either improved or remained stable in most patients. While seven patients showed a robust response, one individual exhibited a suboptimal clinical and biochemical clinical outcome. Overall, the therapy was well-tolerated, with a favorable safety profile and few adverse events.
Conclusions: In this real-world cohort, olipudase alfa was safe and effective in improving clinical and biochemical markers of ASMD, consistent with results from pivotal clinical trials. However, the observed variability in individual responses emphasizes the importance of personalized monitoring and tailored management strategies.
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BibTeX
@article{gragnaniello2026olipudase,
title = {{Olipudase alfa for acid sphingomyelinase deficiency: Evidence of efficacy from a compassionate use program}},
author = {Vincenza Gragnaniello and Veronica Maria Tagi and Francesca Carubbi and Antonio Barbato and Michelina Sibilio and Simona Fecarotta and Maria Grazia Pappalardo and Irene Motta and Annalisa Sechi and Maurizio Scarpa and Andrea Pession and Laura Fiori and On Behalf Of The SIMMESN Italian Enzyme Replacement Therapy Study Group},
journal = {Molecular Genetics and Metabolism Reports},
year = {2026},
month = oct,
doi = {10.1016/j.ymgmr.2026.101372},
url = {https://doi.org/10.1016/j.ymgmr.2026.101372},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Olipudase alfa for acid sphingomyelinase deficiency: Evidence of efficacy from a compassionate use program
AU - Vincenza Gragnaniello
AU - Veronica Maria Tagi
AU - Francesca Carubbi
AU - Antonio Barbato
AU - Michelina Sibilio
AU - Simona Fecarotta
AU - Maria Grazia Pappalardo
AU - Irene Motta
AU - Annalisa Sechi
AU - Maurizio Scarpa
AU - Andrea Pession
AU - Laura Fiori
AU - On Behalf Of The SIMMESN Italian Enzyme Replacement Therapy Study Group
PY - 2026
DA - 2026/10/20
JO - Molecular Genetics and Metabolism Reports
DO - 10.1016/j.ymgmr.2026.101372
UR - https://doi.org/10.1016/j.ymgmr.2026.101372
AB - Background: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by mutations in the SMPD1 gene, leading to systemic accumulation of sphingomyelin, primarily affecting the liver, spleen, lungs, and central nervous system (CNS). Olipudase alfa represents the first approved enzyme replacement therapy (ERT) targeting the non-neurological manifestations of ASMD. This study evaluates real-world safety and efficacy data of olipudase alfa in a cohort of Italian patients. Methods: We retrospectively analyzed clinical, radiological, and laboratory data from 8 Italian patients (5 pediatric, 3 adult) with chronic visceral or chronic neurovisceral ASMD. All patients received olipudase alfa through a compassionate use program between December 2021 and November 2023. Data was collected at baseline, 3, 6, 9, 12, and 15 months of treatment. Results: At baseline, the cohort exhibited hepatosplenomegaly, interstitial lung disease, dyslipidemia, cytopenias, and hypertransaminasemia. Treatment led to significant improvements in hematological parameters, lipid profiles, and liver enzymes. A marked reduction in lyso-sphingomyelin levels was observed, alongside a decrease in spleen and liver volumes. Pulmonary function either improved or remained stable in most patients. While seven patients showed a robust response, one individual exhibited a suboptimal clinical and biochemical clinical outcome. Overall, the therapy was well-tolerated, with a favorable safety profile and few adverse events. Conclusions: In this real-world cohort, olipudase alfa was safe and effective in improving clinical and biochemical markers of ASMD, consistent with results from pivotal clinical trials. However, the observed variability in individual responses emphasizes the importance of personalized monitoring and tailored management strategies.
SN - 2214-4269
ER -