olipudase alfa (Xenpozyme)

The Scottish Medicines Consortium (SMC) has completed its initial assessment of the evidence for the above product using the ultra-orphan framework:

Indication under review: As an enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.

Key points:

• ASMD is a chronic disorder with highly variable symptoms ranging from severe, life-threatening complications early in life, to mild ones. Morbidities include splenomegaly, hepatomegaly, liver dysfunction, pulmonary impairment, thrombocytopenia and neurologic manifestations. Growth restriction during childhood and bone disease are also common features of chronic ASMD. Mortality in ASMD is most frequently due to respiratory failure or liver failure; many patients do not survive into adulthood. There are currently no treatments available and patients are managed with supportive care.
  
  
• In a double-blind, phase II/III study in adult patients with ASMD type A/B or type B, olipudase alfa significantly improved lung function and reduced spleen and liver volumes compared with placebo after 52 weeks. Data from an open-label, single-arm, phase I/II study in paediatric patients with ASMD type A/B or type B treated with olipudase alfa suggest similar improvements from baseline at week 52.
  
  
• There are limited data available in small numbers of patients. Key data in paediatric patients are uncontrolled and efficacy was assessed as exploratory outcomes only. There are limited longer-term efficacy and safety data available for olipudase alfa and some uncertainty about maintenance of effects and long-term safety, and there are no data to support a mortality benefit with olipudase alfa.
  
  
• The cost of olipudase alfa in relation to its benefit remains exceptionally high and there are outstanding uncertainties relating to clinical and quality of life data used in the economic model.

_______________________________________________________________________________________________________________________________________

From 23 February 2024 olipudase alfa (Xenpozyme) can be prescribed within the ultra-orphan pathway while further evidence on its effectiveness is generated. At the end of the data collection period the company will provide an updated submission for reassessment to allow a decision on its routine use in NHSScotland.