1 Recommendations

1.1

Asfotase alfa is recommended as an option for treating paediatric‑onset hypophosphatasia if the person's symptoms started before or at birth (perinatal onset) or between the ages of 0 and 6 months (infantile onset). It is also recommended for people whose symptoms started between the ages of 6 months and 17 years (juvenile onset) only if:

they are aged 1 year to 4 years and have:
- not reached expected developmental gross motor milestones for their age or
- continuing or recurring significant musculoskeletal pain that affects daily activities and quality of life, and has not improved after 2 different types of painkiller recommended by a national pain specialist
they are aged 5 years to 18 years and have:
- limited mobility assessed by a specialist using the modified Bleck Ambulation Efficiency Score and a Bleck score between 1 and 6 or
- continuing or recurring significant musculoskeletal pain that affects daily activities and quality of life, and has not improved after 2 different types of painkiller recommended by a national pain specialist
they are over 18 years and have 2 or more of the following:
- current fractures with a history of non-traumatic, recurring or non- or poorly healing fractures
- limited mobility assessed by a specialist using the modified Bleck Ambulation Efficiency Score and a Bleck score between 1 and 6
- continuing or recurring significant musculoskeletal pain that affects daily activities and quality of life, and has not improved after 2 different types of painkiller recommended by a national pain specialist.
  
  Asfotase alfa is only recommended if the company provides it according to the commercial arrangement.

Why the committee made this recommendation

This evaluation 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 how calcium and phosphorous are deposited in developing bones and teeth. It includes perinatal-, infantile- and juvenile‑onset forms of the disease. There are limited treatment options and it can substantially affect the lives of people with the condition and their families and carers. People with perinatal- or infantile‑onset hypophosphatasia can have breathing complications, craniosynostosis (when the bones in a baby's skull join together too early) and pressure around the brain. The risk of death in the first year of life in these populations is high. The risk of death is lower for people with juvenile‑onset hypophosphatasia. But, juvenile‑onset hypophosphatasia can be associated with severe symptoms that affect quality of life, including impaired mobility, pain and regular fractures. Because of the 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. In juvenile‑onset hypophosphatasia, asfotase alfa is likely to improve outcomes including mobility, pain and health-related quality of life compared with best supportive care.

In perinatal- and infantile‑onset populations, the cost-effectiveness estimates are within the range that NICE considers an acceptable use of NHS resources. So asfotase alfa is recommended for all people in these groups.

In juvenile‑onset populations, the cost-effectiveness estimates are within the range that NICE considers an acceptable use of NHS resources when symptoms are more severe. So asfotase alfa is only recommended for juvenile‑onset hypophosphatasia with severe symptoms.