Rare diseases Xagena

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Xagena Newsletter

Asfotase alfa for the treatment of paediatric-onset hypophosphatasia

Hypophosphatasia ( HPP ) is a rare inheritable disease that results from loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase ( TNSALP ).

Therapeutic options for treating the underlying pathophysiology of the disease have been lacking, with the mainstay of treatment being management of symptoms and supportive care.

Hypophosphatasia is associated with significant morbidity and mortality in paediatric patients, with mortality rates as high as 100% in perinatal-onset hypophosphatasia and 50% in infantile-onset hypophosphatasia.

Subcutaneous Asfotase alfa ( Strensiq ), a first-in-class bone-targeted human recombinant TNSALP replacement therapy, is approved in the European Union ( EU ) for long-term therapy in patients with paediatric-onset hypophosphatasia to treat bone manifestations of the disease.

In noncomparative clinical trials in infants and children with paediatric-onset hypophosphatasia, Asfotase alfa rapidly improved radiographically-assessed rickets severity scores at 24 weeks ( primary timepoint ) as reflected in improvements in bone mineralization, with these benefits sustained after more than 3 years of treatment.

Furthermore, patients typically experienced improvements in respiratory function, gross motor function, fine motor function, cognitive development, muscle strength ( normalization ) and ability to perform activities of daily living, and catch-up height-gain.

In life-threatening perinatal and infantile hypophosphatasia, Asfotase alfa also improved overall survival.

Asfotase alfa was generally well tolerated in clinical trials, with relatively few patients discontinuing treatment and most treatment-related adverse events being of mild to moderate intensity.

Thus, subcutaneous Asfotase alfa is a valuable emerging therapy for the treatment of bone manifestations in patients with paediatric-onset hypophosphatasia. ( Xagena )

Scott LJ, Drugs 2016;76:255-262