Strensiq Receives Marketing Approval in Japan for Treatment of Patients with Hypophosphatasia

Alexion Pharmaceuticals, Inc.

announced today that Japan's Ministry of Health, Labour and Welfare (MHLW) approved the Company's New Drug Application (NDA) for the use of Strensiq® (asfotase alfa) as a treatment for patients in Japan with hypophosphatasia (HPP), a life-threatening, ultra-rare metabolic disorder. Strensiq, a bone-targeted enzyme replacement therapy, is the first therapy approved in Japan for the treatment of patients with HPP. Alexion expects that initial patients with HPP in Japan will start commercial treatment with Strensiq by late Q3 2015. "The rapid approval of the Strensiq NDA in Japan underscores the devastating nature of HPP and the life-transforming impact that Strensiq can provide to Japanese patients living with HPP," said David Hallal, Chief Executive Officer of Alexion. "We are delighted that this regulatory approval in Japan marks the first treatment option for patients with HPP, and we look forward to urgently working with the healthcare authorities to make Strensiq available to Japanese patients who can benefit from this therapy. I would also like to thank the investigators, patients, and their families in Japan who participated in the clinical trial that led to this approval." HPP is a genetic, progressive, ultra-rare metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications. It is characterized by defective bone mineralization that can lead to deformity of bones and other skeletal abnormalities, as well as systemic complications such as profound muscle weakness, seizures, pain, and respiratory failure leading to premature death in infants.1-5 As reflected in the prescribing information in Japan, infants with HPP treated with Strensiq had 84% overall survival, as estimated by Kaplan-Meier analysis, at 168 weeks. "Hypophosphatasia is an ultra-rare disease with diverse clinical symptoms that may be difficult to diagnose. It can be a lethal disease in Japanese newborns and infants which has led to significant challenges since there have been no approved treatment options," said Professor Ozono, Department of Pediatrics Osaka University. "I am greatly delighted that the first treatment has been approved for HPP. The patients and physicians in Japan who participated in the Strensiq clinical trials have played a critical role in generating valuable data and we appreciate their contributions in enabling the approval of Strensiq. I look forward to using Strensiq in clinical practice and continuing to advance the understanding of HPP diagnosis and treatment." "Today's approval marks a major turning point for patients and their families in Japan who have waited a long time for a treatment for hypophosphatasia," said Mr. Hara, Director of HypoPhosPhatasia Support Association of Japan. "The approval of Strensiq offers great hope to patients who previously suffered in the absence of an effective therapy, as well as to the healthcare professionals and families who care for and support them." Alexion has submitted a Biologics License Application for Strensiq with the U.S. Food and Drug Administration, which was accepted for priority review, and received a positive CHMP opinion recommending marketing authorization for Strensiq for patients with pediatric-onset HPP in Europe. Regulatory decisions in the U.S. and Europe are expected in the second half of 2015. Clinical Data The approval of Strensiq in Japan was based on clinical data from three pivotal prospective studies and their extensions, a retrospective natural history study in infants, and one investigator-sponsored study in Japan. The pivotal studies comprised 71 patients, including five Japanese patients, with infantile and juvenile-onset HPP (ages 1 day to 65 years). Study results showed that patients with infantile-onset HPP (ages ≤5 years at enrollment) treated with Strensiq demonstrated rapid and sustained improvements in bone mineralization, as measured by the Radiographic Global Impression of Change (RGI-C) scale, which evaluates the severity of rickets based on X-ray images. In addition, infants with HPP treated with Strensiq had 84% overall survival, as estimated by Kaplan-Meier analysis, at 168 weeks. Patients with juvenile-onset HPP treated with Strensiq demonstrated superior improvements in bone health compared to a control group of HPP patients selected from a natural history database, as well as improvements in ambulation, physical function and growth. The most frequently reported adverse events observed with Strensiq treatment in clinical studies were injection site reactions and injection-associated reactions. Most of these adverse events were mild to moderate in severity. Serious injection-associated reactions were reported in two patients, with neither patient discontinuing Strensiq treatment: one patient with infantile-onset HPP reported fever and chills, and one patient with juvenile-onset HPP reported numbness of lips, leg pain, chills, and headache.