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

Year: 2025

Type: article

Abstract: Hypophosphatasia (HPP) is a rare, inherited metabolic bone disease with a high degree of morbidity and mortality in children. Asfotase alfa is an enzyme replacement therapy for HPP reimbursed in the UK since 2017 under a Managed Access Agreement (MAA). This analysis assessed the effectiveness and safety of asfotase alfa in children < 18 years of age. The MAA was a prospective, longitudinal data collection in children with paediatric-onset HPP. Effectiveness outcomes were evaluated in children who were treated with asfotase alfa for ≥ 6 months. Data were collected on respiratory support, growth, mobility, motor development, analgesic use, quality of life, and safety at enrolment and throughout the 5-year MAA. Twenty-four children enrolled in the MAA and 20 were included in the analysis. Twelve children had received asfotase alfa before enrolment through a clinical trial or compassionate use program. From baseline to month 60, the median (minimum, maximum) change in height and weight Z-scores were 0.20 (− 0.9, 1.2; n = 6) and − 0.5 (− 1.9, 1.5; n = 6), respectively. The median (minimum, maximum) percent of predicted distance walked in the 6-Minute Walk Test increased by 3.8% (− 8.6, 4.3; n = 5) at month 3 and was sustained through follow-up. Median (minimum, maximum) child- and parent-reported Pediatric Quality of Life Inventory scores were 59.2 (15.2, 91.3; n = 11) and 53.4 (16.3, 100.0; n = 18) at baseline and increased by 21.7 (5.4, 37.0; n = 3) and 16.3 (9.8, 45.7; n = 4) at month 60, respectively. Treatment-naïve children had a greater clinical response than treatment-experienced participants, who maintained their status. No deaths occurred in the study. The most common adverse events were injection site reactions, reported in 8/24 participants (33.3%). This analysis confirmed the clinical benefit of asfotase alfa in children with HPP. Asfotase alfa was well tolerated, with no new safety signals identified. Hypophosphatasia is a rare bone disease that can develop in people of all ages, including children. The signs and symptoms of hypophosphatasia can vary depending on the age of the patient. Children with hypophosphatasia may have pain, poor growth, and overall poor quality of life, as well as difficulty walking, moving, or maintaining good posture. Asfotase alfa (Strensiq®) is a drug that helps treat the cause of hypophosphatasia. The Managed Access Agreement was implemented to see if asfotase alfa helps improve the signs and symptoms of hypophosphatasia in children, and to assess the impact of any unwanted effects of treatment. Children who took the drug had improved physical development through up to 5 years of follow-up. They had improvements in height and weight, ability to walk, and other measures of body movement. Children taking the drug also had improved quality of life after starting treatment with asfotase alfa. Children said their quality of life improved after taking the drug for 6 months. Their parents reported that it took 2.5 years for their children’s quality of life to improve. One third of children taking asfotase alfa had a skin reaction at the site of injection, which was the most common side effect reported. Overall, asfotase alfa has an established and well-described safety profile and can help improve physical functioning and quality of life in children with hypophosphatasia.

Source: Advances in Therapy

DOI: 10.1007/s12325-025-03225-4