Olipudase alfa for acid sphingomyelinase deficiency: Evidence of efficacy from a compassionate use program

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.

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.

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.

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.