Alexion Pharmaceuticals announced completion of the rolling submission of a Biologics Licence Application (BLA) to the US Food and Drug Administration (FDA) for asfotase alfa, an investigational, first-in-class enzyme replacement therapy for the treatment of hypophosphatasia (HPP). 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.

“Completion of the rolling BLA is another step forward in our goal to bring this highly innovative potential treatment to patients with HPP who currently have no approved treatment options,” said Leonard Bell, MD, chairman and chief executive officer of Alexion. “Our goal in all territories is to continue to work with regulatory authorities to obtain marketing authorisations for asfotase alfa and to bring this important therapy to patients with HPP as quickly as possible.”

The BLA submission includes data from 71 treated patients with HPP enrolled in three prospective studies and their extensions, as well as a retrospective natural history study in infants with HPP and a separate retrospective natural history study in juveniles with HPP.

In 2013, the FDA granted Breakthrough Therapy designation for asfotase alfa and in April 2014, Alexion initiated the rolling submission of the BLA.

HPP is a genetic, chronic and progressive ultra-rare metabolic disease characterized by defective bone mineralization 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.1 HPP is classified by the age of the patient at the onset of symptoms of the disease, and infantile- and juvenile-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 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.6 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, 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 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 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.