Alexion is developing asfotase alfa as a potential treatment for HPP. Asfotase alfa was used on an investigational basis in the reported study. The U.S. Food and Drug Administration (FDA) recently designated asfotase alfa a Breakthrough Therapy for the treatment of patients with HPP whose first signs or symptoms occurred prior to 18 years of age, including perinatal-, infantile-, and juvenile-onset forms of the disease.About the Phase 2 Trial of Asfotase Alfa in HPP Results were presented from an ongoing multinational, Phase 2, open-label study that enrolled 15 infants and children with HPP (age 5 years or younger) representing a range of HPP characteristics; of this number, 13 patients were included in the Week 24 primary analysis. The median patient age at baseline was 21.14 weeks (range: 0.1-304.0 weeks), and all patients had experienced symptoms of HPP prior to 6 months old. 1 The primary efficacy endpoint of the study was change in skeletal manifestations of HPP over time. The analysis presented today measured this endpoint as changes in the severity of rickets (softening and weakening of bones, which is unrelated to nutrition in patients with HPP) from baseline to Week 24, as assessed by the Radiographic Global Impression of Change (RGI-C) scale, a 7-point scale in which a rating of -3 represents severe worsening and a rating of +3 indicates near or complete healing. Response to treatment was defined as change from baseline in RGI-C of two or more points. Secondary endpoints included changes in respiratory support status, overall survival, and safety and tolerability. Interim results presented today showed that the 13 evaluable patients treated with asfotase alfa had a significant improvement from baseline to Week 24 in skeletal mineralization, with a mean (standard deviation) increase in RGI-C score of 1.74 (1.107) and a median increase of 2.00 (p=0.001). Response to asfotase alfa therapy was evident as early as 12 weeks, with improvement continuing to Week 48. Eight of 12 evaluable patients were characterized as responders (defined as an RGI-C score of +2 [substantial healing] or greater) at Week 24, and all 10 of the evaluable patients at Week 48 were responders. Three patients had RGI-C scores of +3, which indicate near complete healing, at both Weeks 24 and 48. 1 Additionally, the majority of patients (12/15) treated with asfotase alfa improved or preserved respiratory function. Among the eight patients who required respiratory support during the trial, five had improved by their last assessment, and four patients no longer required any support. The overall survival rate, another secondary endpoint, at 48 weeks was 93%. One patient in the study withdrew consent after receiving two doses of asfotase alfa; this patient later died from disease-related complications; the patient’s death was deemed unrelated to the study drug. 1 Asfotase alfa was well-tolerated in the study with no deaths, serious adverse events or discontinuations of therapy deemed related to treatment. The most common adverse events were mild to moderate injection site reactions, reported in 10 of the 15 patients (66.7%). These reactions included redness, (46.7%), discoloration, (26.7%), and hardening of the skin (13.3%). The trial continues to enroll patients and patients continue on treatment. 1 About Hypophosphatasia (HPP) HPP is a chronic, life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. 3-6 HPP is caused by a genetic deficiency of an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), which causes life-long abnormalities in metabolism of two minerals, calcium and phosphate, leading directly to the debilitating morbidities and premature mortality of the disease. 3 The genetic deficiency in HPP can affect people of all ages. 3 HPP is traditionally classified by the age of the patient at the onset of the disease. Patients with perinatal-onset HPP manifest their first signs of disease in utero or at birth. This form of the disease is usually lethal and often leads to death in utero. Those patients who survive birth often have severely compromised respiratory function. 7 Patients with infantile-onset HPP develop their first signs or symptoms of HPP before 6 months of age. Individuals with this form of disease develop skeletal abnormalities and may present with failure to thrive and respiratory failure within the first 6 months of post-natal life. The prognosis of these patients is very poor with mortality estimated at 50%. 3 Patients with juvenile-onset HPP exhibit their first signs or symptoms of HPP after 6 months of age and before 18 years of age. Individuals with this form of the disease are at risk for respiratory complications, painful fractures, and profound muscle weakness and can have delayed acquisition of age-appropriate motor skills due to hypo-mineralization and muscle weakness leading to need for walking assistance; some may never walk. 3 About Asfotase Alfa Asfotase alfa is an investigational, highly innovative, first-in-class targeted enzyme replacement therapy. Asfotase alfa is designed to address the underlying cause of HPP by normalizing the genetically defective metabolic process, and preventing or reversing the severe and potentially life-threatening complications of life-long dysregulated mineral metabolism.