EU/3/14/1351: Orphan designation for the treatment of X-linked hypophosphataemia

X-linked hypophosphataemia is a type of hereditary disorder characterised by low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral essential to build bones and teeth and to maintain their strength. Phosphate levels are largely controlled by the kidneys, which eliminate excess phosphate in urine or reabsorb this mineral into the bloodstream when needed.

Patients with X-linked hypophosphataemia have high levels of a protein called fibroblast growth factor 23 (or FGF23). FGF23 signals the kidneys to stop reabsorbing phosphate into the bloodstream. If levels of FGF23 are high, the kidneys stop reabsorbing phosphate which is then eliminated from the body in the urine leading to low levels of phosphate. As a result, the disease causes delays in children's growth, bone pain and bone deformities (a disorder commonly known as 'rickets').

X-linked hypophosphataemia is a long-term debilitating condition due to bone deformities.

At the time of designation, X-linked hypophosphataemia affected between 0.002 and 0.04 in 10,000 people in the European Union (EU). This was equivalent to a total of between 100 to 2,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of designation, there were no satisfactory methods of treatment for X-linked hypophosphataemia in the EU. Patients with the disease were given phosphate by mouth to try to improve growth, and bone pain.

This medicine is a 'monoclonal antibody', a type of protein designed to recognise and attach to the FGF23 protein. By attaching to the FGF23 protein, the medicine is expected to 'neutralise' its activity leading to the kidneys being able to reabsorb phosphate and restore normal levels of phosphate in the blood. This is expected to improve the symptoms of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with X-linked hypophosphataemia were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for X-linked hypophosphatemia. Orphan designation of the medicine had been granted in the United States of America for X-linked hypophosphatemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 September 2014 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.