Endocrine Abstracts

Objective: To describe outcomes among children with hypophosphatasia (HPP) receiving asfotase alfa.

Methods: This prospective, real-world study used data from all children with HPP receiving asfotase alfa in the UK Managed Access Agreement (MAA) to assess functional, health-related quality-of-life, and safety outcomes. Visits occurred at MAA enrolment, 3 and 6 months after enrolment, and every 6 months thereafter. Assessments at visits were age appropriate: Brief Assessment of Motor Function (BAMF), 1–4 years; Pediatric Quality of Life Inventory (PedsQL), 2–18 years for parent-reported and 5–18 years for child-reported; and modified Bleck and 6-Minute Walk Test (6MWT), 5–18 years. Values, including at first assessment, are presented as median (min, max; n); outcomes from first assessment to 48 months (BAMF: 36 months) are presented as median change (95%CI; n).

Results: All 24 children enrolled received ≥1 asfotase alfa dose; the study population comprised 20 with ≥6 months’ exposure (9 male [45%]; 12 initiating asfotase alfa pre-MAA enrolment [60%]). Age at enrolment was 4.17 (0, 17) years; asfotase alfa treatment duration before enrolment was 3.67 (0.53, 10.10) years. Height Z-score at first assessment was −2.42 (−9.53, −0.28; n=20) and changed by 0.34 (95%CI: −0.34, 1.35; n=12); weight Z-score was −1.86 (−4.93, 1.43; n=20) and changed by 0.20 (95%CI: −1.06, 0.98; n=12). BAMF scores for lower extremities (LEs) and upper extremities (UEs) were 6 (0, 10; n=7) and 9 (0, 9; n=7), respectively, and improved for LEs (7 [95%CI: 3.19, 11.84]; n=3) and UEs (7 [95%CI: 3.19, 11.84]; n=3). Parent- and child-reported PedsQL scores were 53.42 (16.30, 100.00; n=18) and 59.24 (15.22, 91.30; n=10), respectively, and improved by 12.97 (95%CI: 1.94, 24.56; n=10) and 13.04 (95%CI: −4.81, 30.04; n=6), respectively. Starting Bleck scores were relatively high (9 [5, 9]; n=14) and remained stable (0 [95%CI: −1.19, 1.32]; n=6). The 6MWT percent predicted values started at 57.89 (12.41, 90.72; n=11) and changed by 3.28 (95%CI: −26.15, 34.13; n=4). Serious adverse events were infrequent (n=9, 16 events), with 1 event (injection site atrophy) related to asfotase alfa.

Conclusion: Asfotase alfa treatment helped children with HPP in the UK MAA maintain stable outcomes.