EU/3/10/778: Orphan designation for the treatment of cystinosis

Cystinosis is an inherited disease in which the amino acid cystine builds up within cells. The cystine forms crystals that can damage the organs, especially the kidneys and the eyes. Cystinosis is caused by abnormalities in a protein called cystinosin, which normally helps to remove excess cystine from cells.

Cystinosis is a long-term debilitating condition which may be life-threatening because it can lead to kidney failure if left untreated.

At the time of designation, cystinosis affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 people*, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, cysteamine bitartrate was authorised in the EU for the treatment of nephropathic cystinosis. This medicine needs to be taken every six hours.

The sponsor has provided sufficient information to show that cysteamine bitartrate (gastroresistant) might be of significant benefit for patients with cystinosis because the medicine is a new formulation of cysteamine bitartrate that is expected to be given less often than the existing medicine. In addition, the new formulation may have a more pleasant odour and taste, making it easier for patients to take the medicine. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Cysteamine bitartrate works by reacting with cystine to form other substances that can then be removed from the cells. As a result, the amount of cystine in the cells is reduced, limiting the amount of organ damage.

The gastroresistant formulation of cysteamine bitartrate allows cysteamine bitartrate to reach the intestine without being broken down in the stomach. Because cysteamine is absorbed better in the small intestine than in the stomach, this enables more cysteamine to be absorbed with the gastroresistant form than with the existing medicine. This is expected to allow patients to take it less often than the existing medicine (every 12 hours rather than every six hours).

The effects of cysteamine bitartrate (gastroresistant) have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with cysteamine bitartrate (gastroresistant) in patients with cystinosis were ongoing.

At the time of submission, cysteamine bitartrate (gastroresistant) was not authorised anywhere in the EU for cystinosis or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2010 recommending the granting of this designation.

Update: Cysteamine bitartrate (gastroresistant) (Procysbi) was authorised in the EU on 6 September 2013 for the treatment of proven nephropathic cystinosis. Cysteamine reduces cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis patients and, when treatment is started early, it delays the development of renal failure.

• 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.