Medical Management of Hypophosphatasia: Review of Data on Asfotase Alfa

Hypophosphatasia (HPP) is a rare, dento-osseous disorder caused by impaired activity of tissue non-specific alkaline phosphatase (TNSALP), a key enzyme in tissue mineralization. This review provides a clinical perspective on the current medical treatment of both children and adults with HPP.

Dental problems, rickets in children, and osteomalacia in adults are common in HPP. However, disease manifestations in individual patients are exceptionally variable. Recent studies broadened our understanding of HPP symptoms. For example, data showed behavioral health challenges in HPP children, and a large, real-world data set from the Global HPP Registry demonstrated that HPP adults regardless of the time of disease onset exhibit significant disease burden and are broadly affected by non-skeletal impairments, such as pain and chronic fatigue. Treatment for HPP relies on the enzyme replacement asfotase alfa. Small, mostly pediatric trials initially established dosing, safety and efficacy of asfotase alfa, and latest data corroborated the long-term safety and efficacy in both children and pediatric-onset adults. Data from several recent observational studies, including the Global HPP Registry, underscored that asfotase alfa improves physical functions, non-skeletal symptoms such as pain, and quality-of-life (QoL) in adults irrespective of age-of-onset. Clinical use of asfotase alfa is based on prescribing information and evidence-based consensus guidelines. However, recommendations for initiation of therapy are just emerging. Alternatives to asfotase alfa remain limited, but a derivative, efzimfotase alfa, currently undergoes clinical testing. Studies in larger HPP patient populations suggest efficacy of enzyme replacement therapy independent of patient age and time of disease onset.