Alexion Pharmaceuticals, a biopharmaceutical company focused on serving patients with severe and rare disorders, announced that Japanese Ministry of Health, Labour and Welfare (MHLW) has granted orphan drug designation (ODD) to asfotase alfa for the treatment of patients with hypophosphatasia (HPP), a genetic, chronic and progressive ultra-rare metabolic disease characterised by defective bone mineralisation. Patients with HPP can experience a range of devastating consequences, including the destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death.1-5 Asfotase alfa is an investigational, highly innovative, first-in-class targeted enzyme replacement therapy designed to address the underlying cause of HPP.

“HPP is a devastating disease for patients and families and there are currently no approved treatment options,” said Martin Mackay, Ph.D., executive vice president, Global Head of R&D at Alexion. “The orphan drug designation granted for asfotase alfa undescores the significant need for an effective treatment option for Japanese patients suffering from this severe, ultra-rare disorder.”

The Ministry of Health, Labour and Welfare, based on the opinion of the Pharmaceutical Affairs and Food Sanitation Council, grants orphan status to drugs and medical devices that treat serious diseases of high unmet medical need that affect fewer than 50,000 patients in Japan. Orphan drug designation provides drug developers with certain benefits and incentives, including priority review for marketing authorisation and a period of 10 years of market exclusivity if regulatory approval is received for the designated indication.

Hypophosphatasia (HPP) is a genetic, chronic and progressive ultra-rare metabolic disease characterised 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, and paediatric-onset HPP is defined as first symptom prior to 18 years of age.

HPP can have devastating consequences for patients at any stage of life. Pediatric patients with HPP have a high mortality rate; mortality in these patients is primarily due to respiratory failure.1,5 In patients surviving to adolescence and adulthood, long-term clinical sequelae include recurrent and non-healing fractures, debilitating weakness, severe pain, and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.

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 normalising the genetically defective metabolic process, and preventing or reversing the severe and potentially life-threatening complications of life-long dysregulated mineral metabolism.

In 2013, the US Food and Drug Administration (US FDA) granted Breakthrough Therapy designation for asfotase alfa. According to the FDA, a Breakthrough Therapy designation is designed to expedite the development of a drug to treat a serious or life-threatening disease when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

In April 2014, Alexion initiated the rolling submission of a Biologics License Application (BLA) for asfotase alfa as a treatment for patients with HPP with the FDA. In July 2014, the Marketing Authorisation Application (MAA) for asfotase alfa was validated and granted accelerated assessment by the European Medicines Agency (EMA).