Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Alexion Pharmaceuticals, Inc'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 mineralisation 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. As reflected in the prescribing information in Japan, infants with HPP treated with Strensiq had 84 per cent 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 paediatrics, 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 US Food and Drug Administration, which was accepted for priority review, and received a positive CHMP opinion recommending marketing authorisation for Strensiq for patients with paediatric-onset HPP in Europe. Regulatory decisions in the US and Europe are expected in the second half of 2015.

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 per cent 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.

HPP is a genetic, chronic and progressive ultra-rare metabolic disease characterized by defective bone mineralisation that can lead to destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death.

HPP is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase (TNSALP). The genetic deficiency in HPP can affect people of all ages. HPP is classified by the age of the patient at the onset of symptoms of the disease, with infantile- and juvenile-onset HPP defined as manifestation of the first symptom prior to 18 years of age.

HPP can have devastating consequences for patients at any stage of life.1 In a natural history study, infants who had their first symptom of HPP within the first 6 months of life had high mortality, with an overall mortality rate of 73 per cent at 5 years. In these patients, mortality is primarily due to respiratory failure. In patients surviving to adolescence and adulthood, long-term clinical sequelae include recurrent and non-healing fractures, profound muscle weakness, debilitating pain and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.

Strensiq (asfotase alfa) is a first-in-class bone-targeted enzyme replacement therapy designed to address the underlying cause of HPP—deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralize bone, thereby preventing serious skeletal and systemic patient morbidity and premature death.

Strensiq has been granted orphan drug designation by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour and Welfare (MHLW). Alexion has submitted a Biologics License Application for Strensiq with the US Food and Drug Administration, which was accepted for priority review, and a Marketing Authorisation Application for Strensiq in Europe is under review.

Alexion is a global biopharmaceutical company focused on developing and delivering life-transforming therapies for patients with devastating and rare disorders.