The European Commission has approved Alexion Pharmaceuticals Inc's Strensiq (asfotase alfa) for long-term enzyme replacement therapy in patients with paediatric-onset hypophosphatasia (HPP) to treat the bone manifestations of the disease.

The summary of product characteristics (SmPC) states that HPP is associated with multiple bone manifestations including rickets/osteomalacia, altered calcium and phosphate metabolism, impaired growth and mobility, respiratory compromise that may require ventilation, and vitamin B6-responsive seizures. The natural history of untreated infant hypophosphatasia patients suggests high mortality if ventilation is required. The SmPC also indicates that 71 per cent of infant patients treated with Strensiq who required ventilation support remain alive and continue on treatment. Strensiq is the first therapy approved in the European Union (EU) for the treatment of patients with HPP, a life-threatening, ultra-rare metabolic disorder. Alexion expects to begin serving patients in Germany in October and is now commencing reimbursement processes with healthcare authorities in each of the major European countries.

“Hypophosphatasia is an extremely rare disorder that can have devastating consequences for patients and families. Without treatment, patients may face significant challenges related to development, growth, and mobility, with an extremely high risk of mortality in infants,” said PD Dr. med Christine Hofmann, Children’s Hospital, University of Würzburg, paediatric rheumatology and osteology section, Würzburg, Germany.

“I am very pleased that patients with paediatric-onset HPP in Europe now have an approved treatment that addresses the underlying cause of their genetic, lifelong metabolic disease by replacing tissue non-specific alkaline phosphatase.”

HPP is a genetic and progressive metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications. It is an ultra-rare disease, which is defined as a disease that affects fewer than 20 patients per one million in the general population. HPP 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. 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 traditionally 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. 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.

"As the first approved treatment for paediatric-onset HPP in Europe, Strensiq is an innovative therapy for patients suffering from this devastating and life-threatening ultra-rare disease. We are pleased that the EU label will allow any patient who had symptoms of HPP prior to the age of 18 to be eligible for treatment,” said David Hallal, chief executive officer of Alexion.

“We are grateful to the investigators, patients, and their families who participated in the clinical trials that made this approval possible and we are now commencing reimbursement processes with healthcare authorities throughout Europe to ensure that patients with paediatric-onset HPP have access to Strensiq, a life-transforming treatment, as quickly as possible.”

The EC approval of Strensiq applies to all 28 EU member states as well as Iceland, Norway, and Lichtenstein and follows the June 2015 positive opinion granted by the Committee for Medicinal Products for Human Use (CHMP). Strensiq has also been approved for the treatment of HPP by the Japanese Ministry of Health, Labour and Welfare and by Health Canada. The FDA granted Breakthrough Therapy designation for Strensiq and accepted Alexion’s Biologics License Application (BLA) for Priority Review.

The approval of Strensiq in the EU was based on clinical data from four pivotal prospective studies and their extensions, comprising 68 patients with pediatric-onset HPP (ranging from newborns to 66 years of age). Study results showed that patients with pediatric-onset HPP 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. Patients in the clinical studies also had improvements in skeletal structure, as demonstrated by x-ray appearance of joints, by histological appearance of bone biopsy material, and by apparent catch-up height-gain.

The most common adverse reactions observed in clinical studies were injection site reactions and injection-associated adverse reactions. Most of these reactions were non-serious and mild to moderate in intensity.

Strensiq is an innovative enzyme replacement therapy designed to address the underlying cause of HPP—a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity. By replacing the defective enzyme, treatment with Strensiq aims to prevent or reverse the mineralisation defects of the skeleton, thereby preventing serious skeletal and systemic morbidity and premature death.