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    Asfotase alfa for treating paediatric-onset hypophosphatasia (review of HST6)

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    1 Recommendations

    1.1 Asfotase alfa is recommended as an option for treating hypophosphatasia, only if:

    • the person's symptoms began:

      • before or at birth (perinatal onset) or

      • between the ages of 0 and 6 months (infantile onset)

    • the company provides it according to the commercial arrangement (see section 2).

    1.2 The committee was minded not to recommend asfotase alfa as an option for treating hypophosphatasia in people whose symptoms started between the ages of 6 months and 17 years (juvenile onset).

    1.3 The committee recommends that NICE requests further clarification and analyses from the company, which should be made available for the second evaluation committee meeting. It should include:

    • Analyses of data specific to juvenile-onset hypophosphatasia, collected during the managed access agreement, the asfotase alfa clinical trial programme and from the Global Hypophosphatasia Registry (ALX-HPP-501), for all relevant outcomes.

    • Comparative efficacy analysis of asfotase alfa and best supportive care in people with juvenile-onset hypophosphatasia for all relevant outcomes.

    • Cost-effectiveness analysis of a population with juvenile-onset hypophosphatasia, where the disease severity of the starting cohort in the model is based on data from people with juvenile-onset hypophosphatasia. That is, the distribution across health states should be specific to people with juvenile-onset hypophosphatasia.

    • Cost-effectiveness analysis of a population with juvenile-onset hypophosphatasia that uses data specific to people with juvenile-onset hypophosphatasia for both the asfotase alfa and best supportive care groups.

    1.4 The managed access agreement reached between NHS England, the company, NICE and a patient organisation states that in the event that NICE do not make a positive recommendation by the expiry of the managed access agreement funding will cease to be available for patients and treatment will cease. Any cessation of treatment for a population not covered by a positive NICE recommendation would be managed between Alexion and NHS England to ensure it is effected in a controlled manner.

    Why the committee made these recommendations

    This guidance reviews the evidence for asfotase alfa for treating paediatric-onset hypophosphatasia (NICE highly specialised technologies guidance 6), including evidence collected as part of the managed access agreement.

    Paediatric-onset hypophosphatasia is a rare genetic condition that affects the way calcium and phosphorous are deposited in developing bones and teeth. There are limited treatment options and it can substantially affect the lives of people with the condition, their families and carers. People with perinatal- or infantile-onset hypophosphatasia can have breathing complications, craniosynostosis (where the bones in a baby's skull join together too early) and pressure around the brain. The risk of death in the first year with perinatal- or infantile-onset hypophosphatasia of life is high and it tends to be more severe than juvenile-onset hypophosphatasia (where symptoms start in childhood after 6 months of age). Because of this difference in severity, the committee considered the 2 populations separately.

    In perinatal- or infantile-onset hypophosphatasia, asfotase alfa is likely to increase how long people live before needing a ventilator and how long people live overall compared with best supportive care. For this population, the cost-effectiveness estimates are below what NICE normally considers an acceptable use of NHS resources. So, asfotase alfa is recommended for perinatal- or infantile-onset hypophosphatasia.

    For juvenile-onset hypophosphatasia, the evidence is uncertain. Asfotase alfa has not been compared with best supportive care in this population. The available evidence from clinical trials and registries was not presented specifically for the subgroup of people with juvenile-onset hypophosphatasia and the company's economic model also did not use data specifically from this group. As a result, the cost-effectiveness estimate in this population is uncertain and unlikely to provide value for money. So, the committee was minded not to recommend asfotase alfa in this subgroup until these uncertainties have been explored further.