velmanase alfa (Lamzede)

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: Treatment of enzyme replacement therapy for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis.

Key points:

• Alpha-mannosidosis is a very rare progressive lysosomal storage disorder which results in the accumulation of mannose-rich oligosaccharides in all tissues leading to cell and tissue dysfunction affecting multiple systems. This causes a broad range of cognitive and physical symptoms which vary widely in range, severity and rate of progression between patients.
  
  
• Evidence from a double-blind, randomised, phase III study demonstrated significant reductions in serum oligosaccharide levels after 52 weeks of treatment with velmanase alfa compared with placebo.
  
  
• The placebo-controlled study was limited by a lack of power calculation and small patient numbers leading to uncertainty in the magnitude of treatment effect. There was no significant improvement in the clinical outcome of 3-minute stair climb test. The 52-week duration was considered too short to adequately assess the longer term benefits of velmanase alfa on clinically relevant outcomes including disease progression and complications as well as long term safety.
  
  
• There were no significant differences between velmanase alfa and placebo for quality of life measurements assessed after 52 weeks.
  
  
• The submitting company has positioned the use of velmanase alfa for patients aged 6 years and over, for whom treatment with allogeneic haematopoietic stem cell transplant (HSCT) is unsuitable/not possible. Although the use of velmanase alfa is not restricted by age, there is agreement generally that HSCT is likely to be targeted towards younger children less than aged 6 years, based on clinical judgement, so HSCT has been excluded as a comparator in this submission.
  
  
• There were a number of uncertainties in the economic analysis, and while this is to be expected to some extent given the sample sizes available from the clinical data, several key assumptions about the utility benefit conferred by treatment with velmanase alfa, the longer-term effect of treatment on quality of life and delays to deterioration in functional status (as determined by walking ability) among responders remain difficult to validate beyond expert opinion.
  
  
• Despite a PAS that improves the cost-effectiveness of velmanase alfa, the treatment’s cost in relation to its health benefits remains high.

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From 4 April 2023 velmanase alfa (Lamzede) 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.