olipudase

Olipudase, also known as olipudase alfa, is a recombinant human enzyme replacement therapy developed to treat acid sphingomyelinase deficiency (ASMD), a lysosomal storage disorder also called Niemann-Pick disease types A, B, and A/B. ASMD arises from deficient activity of the enzyme acid sphingomyelinase, leading to accumulation of sphingomyelin in lysosomes and widespread organ involvement, particularly in the liver, spleen, lungs, and bone marrow.

Mechanism and purpose: Olipudase alfa provides functional acid sphingomyelinase to degrade sphingomyelin, reducing lysosomal storage and helping to mitigate somatic manifestations of ASMD. Because the blood-brain barrier limits access to the central nervous system, enzyme replacement therapy primarily targets non-neurological (somatic) symptoms.

Indications and patient population: The therapy is intended for the treatment of non-neurological manifestations of ASMD. Neurological symptoms, especially in Niemann-Pick disease type A, are typically not addressed by enzyme replacement therapy due to limited CNS penetration.

Administration and dosing: Olipudase alfa is given by intravenous infusion, usually on a biweekly schedule, with dose adjustments based on body weight and tolerability. Infusion-related reactions are managed with standard clinical practices, including premedication and gradual infusion rates as needed.

Clinical evidence and outcomes: In phase 2 and 3 studies, olipudase alfa has shown reductions in liver and spleen volumes and improvements in pulmonary function and functional capacity in affected individuals. Additional benefits have been reported in hematologic and hepatic parameters, with responses observed across a range of disease severities.

Safety and monitoring: Common adverse events include infusion-related reactions, fever, headache, and fatigue. Some patients develop anti-drug antibodies; monitoring typically covers liver enzymes, respiratory status, and signs of hypersensitivity during infusions.

Regulatory status: Regulatory approvals for olipudase alfa vary by country, with approvals granted in some jurisdictions for non-neurological ASMD manifestations and ongoing regulatory review in others. See also Niemann-Pick disease and lysosomal storage disorders.