EU/3/18/1983: Orphan designation for the treatment of pyridoxamine 5'-phosphate oxidase deficiency

Pyridoxamine 5'-phosphate oxidase deficiency is a hereditary disease affecting children. It is caused by a defect in the PNPO gene needed to produce an enzyme known as pyridoxine 5'-phosphate oxidase. This enzyme is required to convert pyridoxine (or vitamin B6) into its active form pyridoxal 5'-phosphate (PLP), which is essential for brain function. Children with the disease do not have enough PLP and this leads to various symptoms, which normally appear shortly after birth, including irritability, inflammation of the lips, conjunctivitis (inflammation of the membrane that lines the eye and the inside of the eyelids), seizures (fits) and other neurological problems.

Pyridoxamine 5'-phosphate oxidase deficiency is a life-threatening disease due to severe problems with brain function.

At the time of designation, pyridoxamine 5'-phosphate oxidase deficiency affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 517,400,000 (Eurostat 2018).

At the time of designation, no satisfactory methods of treatment were authorised in the EU for pyridoxamine 5'-phosphate oxidase deficiency. Products containing PLP were given to patients but existing formulations for use by mouth were not appropriate for use in children and for managing seizures associated with the disease.

This medicine is expected to work by replacing the missing PLP in patients with pyridoxamine 5'-phosphate oxidase deficiency. It is intended to be given by injection into a vein, allowing for immediate action which is important in the treatment of seizures associated with the disease.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with pyridoxamine 5'-phosphate oxidase deficiency had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for pyridoxamine 5'-phosphate oxidase deficiency. Orphan designation of pyridoxal 5'-phosphate had been granted in the EU for the condition and in the United States for the treatment of seizures associated with the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 January 2018 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.