Alexion Pharmaceuticals, a bio pharmaceuticals company, has submitted a New Drug Application (NDA) for asfotase alfa, an investigational, first-in-class targeted enzyme replacement therapy for the treatment of hypophosphatasia (HPP), to Japan’s Ministry of Health, Labour and Welfare (MHLW). HPP is a genetic, chronic and progressive ultra-rare metabolic disease that can lead to destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death.

“The NDA submission for asfotase alfa is a critical step toward bringing this highly innovative and much-needed potential treatment to patients in Japan suffering from HPP,” said Leonard Bell, M.D., chairman and chief executive officer of Alexion. “If approved, asfotase alfa would be the first therapy for patients with this devastating and life-threatening disorder.”

The MHLW submission includes positive data from 71 patients with HPP (ranging from newborns to 66 years of age), including Japanese patients, enrolled in three pivotal prospective studies and their extensions, as well as a retrospective natural history study in infants.

In September 2014, the MHLW granted orphan drug designation (ODD) to asfotase alfa for the treatment of patients with HPP. As a result, the NDA for asfotase alfa will receive priority review for marketing authorisation, and, if approved, asfotase alfa would have 10 years of market exclusivity for the designated indication.

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.1-5

HPP is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase (TNSALP).1,2 The genetic deficiency in HPP can affect people of all ages.1 HPP is classified by the age of the patient at the onset of symptoms of the disease, and pediatric-onset HPP is 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 Pediatric patients with HPP have a high mortality rate, with 73 per cent mortality reported in a natural history study at 5 years.6 In these patients, mortality is primarily due to respiratory failure.1,5,7 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 aiming to restore the genetically defective metabolic process, thereby 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 Licence Application (BLA) for asfotase alfa as a treatment for patients with HPP with the US Food and Drug Administration (US FDA). In July 2014, the Marketing Authorisation Application (MAA) for asfotase alfa was validated and granted accelerated assessment by the European Medicines Agency (EMA).