EU/3/16/1677: Orphan designation for the treatment of periodic paralysis

Periodic paralysis is a group of inherited muscle disorders that causes periodic attacks of weakness or paralysis (inability to move), which resolve spontaneously after some time. The attacks can be triggered by stress, excitement, physical activity, heat or cold. Muscle weakness can affect a small group of muscles, or can be more generalised and affect the whole body.

Periodic paralysis is caused by abnormalities in the ion channels, tiny pores in the muscle cells that control the passage of charged particles (ions) such as sodium or chloride and play a key role in the contraction and relaxation of muscles.

Periodic paralysis is a long-term debilitating disorder due to permanent muscle weakness, muscle pain and the need for mobility aids. It can be life threatening because of the risk of heart arrhythmias (unstable heartbeat) which could lead to a heart attack.

At the time of designation, periodic paralysis affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 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 513,700,000 (Eurostat 2016).

At the time of submission, no satisfactory methods were authorised in the EU for the treatment of periodic paralysis.

The way this medicine works in periodic paralysis is not fully understood but it is thought to increase the removal of bicarbonate, sodium and potassium through the urine. This increases the acidity of the body (a condition known as 'metabolic acidosis'), which studies show can help normalise the function of the ion channels in muscle cells, thus regulating muscle contraction.

The effects of diclofenamide have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with diclofenamide in patients with periodic paralysis had finished.

At the time of submission, diclofenamide was authorised in the United States for the treatment of primary periodic paralysis.

At the time of submission, diclofenamide was not authorised anywhere in the EU for periodic paralysis. Orphan designation of diclofenamide had been granted in the EU for periodic paralysis and in the United States for primary periodic paralyses.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 May 2016 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.