Asfotase alfa safe, effective for hypophosphatasia

Asfotase alfa improved respiratory, skeletal and physical symptoms of hypophosphatasia, according to the results of a study conducted in Japan.

“The prognosis associated with the most severe form of [hypophosphatasia] is very poor, because such patients suffer from respiratory failure due to marked hypomineralization of bones,” Taichi Kitaoka, of the department of pediatrics at Osaka University Graduate School of Medicine, and colleagues wrote. “A clinical trial of [asfotase alfa] has reported it to be safe and effective for 10 patients with perinatal, infantile and childhood [hypophosphatasia]. Moreover, a long-term study of asfotase alfa demonstrated the improvement of mineralization, respiratory function and survival rate in 37 patients with perinatal and infantile [hypophosphatasia] compared to 48 historical controls. However, more experience is needed to better establish its safety and efficacy.”

Kitaoka and colleagues performed an open-label, multicenter prospective trial on 13 patients with hypophosphatasia (9 female, 4 male). Patients were aged between 0 days and 34 years. All patients had ALPL gene mutations and were treated with 2 mg/kg of subcutaneous asfotase alfa  three times weekly. Six patients had perinatal hypophosphatasia, five had childhood disease and one each had childhood and adult disease. The primary outcome was safety as determined by adverse events and laboratory data, and the secondary outcome was efficacy measured by overall survival, respiratory status, rickets severity and gross motor development.

Overall, researchers wrote, there were 195 adverse events, 91% of which were mild; 7% were moderate and 2% were severe. Kitaoka and colleagues reported that 104 (53%) adverse events were considered related to asfotase alfa. Injection site reactions were the most common treatment-related adverse events (88 events in seven patients). Researchers reported six severe adverse events in two patients, including convulsion and hypocalcemia in a patient with perinatal hypophosphatasia. Three infants had hypercalcemia and/or hyperphosphatemia and were given low-calcium and/or low-phosphate formula. Radiographic findings, developmental milestones and respiratory function improved overall.

“It is strongly suggested that [asfotase alfa] treatment of patients with [hypophosphatasia] improves prognosis,” Kitaoka and colleagues wrote. “The treatment has been called transformative. Thus, the early diagnosis of [hypophosphatasia] is important in this situation. We hope to develop a guide on how to manage patients with [hypophosphatasia] in terms of diagnosis and treatment in the near future.” – by Andy Polhamus

Disclosure: Kitaoka reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.