OBJECTIVES: In 2017, a managed access agreement (MAA) was developed establishing coverage in England of asfotase alfa, an enzyme-replacement therapy for paediatric-onset hypophosphatasia, an ultra-rare condition associated with significant mortality in infants and morbidity in children and adults. The MAA specified an outcomes-based agreement, conditioning payments on realization of benefits that were modelled in a cost-effectiveness analysis (CEA) of asfotase alfa vs best supportive care. Such benefits included (i) for patients starting treatment at ages <2 years, invasive-ventilation free survival at age 2 and (ii) for patients starting treatment at ages ≥2, quality-adjusted life year (QALY) gains based on health-utility improvements (PedsQL for ages 2-<18 years and EQ-5D-5L for ages ≥18 years). In this analysis, benefits observed under the MAA were compared against cost-effective benefit levels from the original CEA, to assess the real-world cost-effectiveness of asfotase alfa.

METHODS:

RESULTS: The MAA enrolled 54 patients from 2017-2022, of whom 2 did not receive treatment and 4 had HPP-unrelated issues preventing analysis of QALY gains. Ten patients started the MAA at ages <2; all 8 who turned age 2 during the MAA were invasive-ventilation free. QALY gains were analyzed in the 38 patients who started treatment at ages ≥2 and the 8 who turned 2 during the MAA. Median follow-up was 27, 45, 54, and 24 months for the 0-1, 2-4, 5-12, and adult baseline-age cohorts. No patients were included for the 13-17 cohort. Median actual-minus-expected QALY gains across the cohorts ranged from -0.13 to +0.48. Overall, 89% of expected QALY gains were realized.

CONCLUSIONS: Benefits of asfotase alfa observed under the MAA were consistent with previous CEA, indicating real-world cost effectiveness.