Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement

Journal article

Introduction: Hypophosphatasia (HPP) is a rare disease caused by deficient tissue–non-specific alkaline phosphatase (ALP) activity. Asfotase alfa is a tissue–non-specific ALP enzyme-replacement therapy which was reimbursed in the UK under a Managed Access Agreement (MAA). This analysis assessed safety and effectiveness of asfotase alfa in adults with HPP. Methods: This prospective, observational data collection included adults with paediatric-onset HPP enroled in the MAA and treated with asfotase alfa for ≥ 6 months to 5 years. Assessments included mobility, pain, and health-related quality of life (HRQoL), each reported at regular intervals through year 3. Analgesic use, fractures, and events of interest (EOIs) were each reported continuously throughout follow-up. Results: Of 28 enroled treated adults, 24 were assessed for effectiveness. Distance walked in the 6-Minute Walk Test was median (min, max) 172.5 m (0.0, 380.0; n = 24) at baseline and improved by 157.3 m (− 171.0, 479.5; n = 16) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n = 24) at baseline and increased to 6.5 (5.0, 9.0; n = 10) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n = 24) at baseline and improved to 4.4 (1.0, 7.8; n = 10) at month 36. During follow-up, 8 participants (33.3%) decreased or discontinued opioid use throughout follow-up and 4 (16.7%) reported fractures. Median (min, max) EQ-5D-3L utility scores improved from 0.21 (− 0.26, 0.60; n = 24) at baseline by 0.15 (− 0.36, 0.91; n = 24) at month 6 and were similar throughout follow-up. Injection site reactions were the most common treatment-related EOI, reported in 17 participants (60.7%). Three participants reported treatment-related serious adverse events. Conclusion: Asfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP.

Authors: Moss, KE; Keen, R; Fang, S; Zygouras, A; Javaid, MK

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Advances in Therapy
• Volume: 42
• Issue: 5
• Pages: 2429-2444
• Publication date: 2025-03-26
• Acceptance date: 2025-03-03
• DOI: 10.1007/s12325-025-03168-w
• EISSN: 1865-8652
• ISSN: 0741-238X
• Language: English
• Keywords: 6-Minute Walk Test; Asfotase alfa; Hypophosphatasia; Rare disease; Quality of life