EU/3/16/1612

On 17 February 2016, orphan designation (EU/3/16/1612) was granted by the European Commission to Retrophin Europe Limited, Ireland, for methyl 3-((2R)-2-hydroxy-4-(((((S)-1-methoxy-1-oxopropan-2-yl) amino)(phenoxy)phosphoryl)oxy)-3,3-dimethylbutanamido)propanoate for the treatment of pantothenate-kinase-associated neurodegeneration.

What is pantothenate-kinase-associated neurodegeneration?

Pantothenate-kinase-associated neurodegeneration (PKAN) is an inherited disease caused by a mutation (change) in the gene that produces an enzyme called pantothenate kinase-2. This enzyme is needed by brain cells for the first step in producing coenzyme A, which is essential for them to function. Patients with the disease cannot produce pantothenate kinase-2, resulting in gradual brain damage. Symptoms of PKAN usually appear in childhood and include severe dystonias (painful muscle spasms) and Parkinson-like effects such as rigidity and slow movement, as well as loss of sight and impaired swallowing.

PKAN is a long-term debilitating and life-threatening disease due to complications of severe muscle spasms that can affect swallowing and lead to pneumonia (infection of the lungs) and malnutrition.

What is the estimated number of patients affected by the condition?

At the time of designation, PKAN affected less than 0.03 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 1,500 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 513,700,000 (Eurostat 2016).

What treatments are available?

No satisfactory methods of treatment for PKAN were authorised in the EU at the time of orphan designation. Patients received supportive therapy including muscle-relaxant medicines and Parkinson medicines to deal with the symptoms.

How is this medicine expected to work?

The enzyme pantothenate kinase-2 converts pantothenate (also called vitamin B5) from food into phosphopantothenate. This is the first of several steps in the production of the essential substance coenzyme A. Because patients with PKAN lack functioning pantothenate kinase-2, the cells cannot produce normal levels of phosphopantothenate that they need to produce coenzyme A.

This medicine provides a source of phosphopantothenate in a form that can be absorbed by cells. This allows brain cells to make the coenzyme A they need, thereby improving the symptoms of the condition.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, a clinical trial with this medicine in healthy volunteer had been completed and clinical trials in patients with PKAN were planned.

At the time of submission, the medicine was not authorised anywhere in the EU for PKAN. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 January 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.