Effects of asfotase alfa in adults with pediatric-onset hypophosphatasia over 24 months of treatment.

Background: Hypophosphatasia (HPP) is a rare, heritable metabolic disorder caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Asfotase alfa (AA) is a human recombinant TNSALP that promotes bone mineralization and is approved to treat eligible patients with HPP.

Methods: This prospective single-center observational study evaluated AA in adults with pediatric-onset HPP over 2 years of treatment (ClinicalTrials.govNCT03418389). Primary outcomes evaluated physical function; secondary outcomes assessed quality of life (QoL) and pain.

Results: The study included 17 females and 5 males (mean age: 48.7 years). Median distance walked in the 6-Minute Walk Test increased significantly from baseline to 12 months (P = 0.034) and results were sustained. Median Timed Up and Go test time significantly decreased from baseline at 12 (P = 0.003) and 24 months (P = 0.005), as did the median chair rise time test at 12 (P = 0.003) and 24 months (P < 0.002). The change from baseline in usual gait speed was significant at 12 (P = 0.003) and 24 months (P = 0.015). Mean dominant and nondominant hand grip strength improved at 24 months (P = 0.029 and P = 0.019, respectively). Median Short Form 36 Physical Component Summary scores significantly improved from baseline at 12 (P = 0.012) and 24 (P = 0.005) months, and median Lower Extremity Functional Scale scores improved from baseline at 12 (P = 0.001) and 24 (P = 0.002) months. No significant change was noted in pain level at these timepoints. While injection site reactions occurred in 86.4 % of the participants, there were no severe side effects or safety findings.

Conclusions: Adults with pediatric-onset HPP treated with AA experienced marked improvement in functional and QoL outcomes that were observed as early as within 3 months of initial treatment and were sustained over 24 months.