CHESHIRE, Conn.--(BUSINESS WIRE)--

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN - News) today announced that asfotase alfa (formerly known as ENB-0040), a highly innovative investigational targeted enzyme replacement therapy, was shown to improve skeletal abnormalities, pulmonary and physical function, and cognitive development in a Phase 2 study of infants and young children with life-threatening hypophosphatasia (HPP). Alexion is developing asfotase alfa as a potential treatment for patients with HPP, an ultra-rare, genetic, life-threatening metabolic disease for which there are currently no approved or effective treatment options. Findings from the study are published in the March 8th issue of the New England Journal of Medicine.

Due to a genetic enzyme deficiency, symptomatic patients with HPP face progressive damage to multiple vital organs including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure.1,2,3,4 About half of newborns with HPP do not survive past one year of age.1

This inborn error of metabolism can cause progressive skeletal deterioration and muscle weakness in severely affected infants and very young children with HPP, leading to respiratory insufficiency and significant mortality, said lead study author Michael P. Whyte, M.D., Medical-Scientific Director, Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis. In this study of patients with severe perinatal and infantile forms of HPP, we saw in nearly all patients striking skeletal healing that included improved bone formation and reduced deformity, as well as improved pulmonary function and motor development. These findings are remarkable given the historically grim outlook for patients with life-threatening HPP.

About the Study

The multinational, open-label Phase 2 study of asfotase alfa enrolled 11 patients with HPP ages 3 years or younger whose symptoms began before the age of 6 months. Patients in the study received asfotase alfa for six months and then had the opportunity to enroll in an open-label extension study.

The primary efficacy endpoint was change in the skeletal manifestations of HPP, as assessed by radiography. Response to treatment was defined as a mean improvement of two or more points, as rated by a panel of three independent radiologists, on a seven-point scale known as the radiographic global impression of change (RGI-C). Skeletal changes were also assessed using a 10-point scale that measured skeletal abnormalities at the wrists and knees. Additional efficacy assessments included evaluations of respiratory status, gross motor function, and cognitive development (Bayley-III scale).

Ten patients completed the six-month study and nine patients are currently participating in the extension study. All patients treated with asfotase alfa demonstrated an improvement in two key biochemical indicators of HPP: blood levels of PPi (inorganic pyrophosphate) and PLP (pyridoxal 5 phosphate). For the primary efficacy endpoint, nine of 10 patients (90%) met the criterion for treatment response by week 24, and eight of nine (89%) achieved treatment response by week 48. Skeletal healing became apparent as early as week 3.

Respiratory function improved in all patients. These improvements were evident as early as week 12. Compared to the 10 of 11 patients who required respiratory support at baseline, at week 48 only three of nine patients required any respiratory support and only one patient remained on full mechanical ventilation. In addition to the improvements in bone mineralization and respiratory function, there were improvements in fine motor, gross motor and cognitive development, as assessed by the Bayley-III instrument, for seven of the eight patients who were evaluated. Whereas at baseline, no patients were able to bear weight through their legs owing to skeletal abnormalities and muscle weakness, at 48 weeks of treatment, seven of nine patients were able to bear weight through their legs.

The most common treatment-related adverse event observed in the study was mild injection-site reaction. Severe adverse events observed in the study were generally consistent with the symptoms expected of patients with severe HPP, including infection, respiratory disorders, and nervous-system complications. One patient died, and this was determined to not be related to study drug.

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New England Journal of Medicine Publishes Data from Phase 2 Study of Asfotase Alfa in Life-Threatening Hypophosphatasia

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