EU/3/10/778 - orphan designation for treatment of cystinosis

Cysteamine bitartrate (gastroresistant) (mercaptamine)

Overview

Cysteamine bitartrate (gastroresistant) has been authorised in the EU as Procysbi since 6 September 2013.

On 20 September 2010, orphan designation (EU/3/10/778) was granted by the European Commission to Raptor Pharmaceuticals Europe BV, the Netherlands, for cysteamine bitartrate (gastroresistant) for the treatment of cystinosis.

This medicine is now known as mercaptamine.

In February 2017, Raptor Pharmaceuticals Europe B.V changed name to Horizon Pharma Europe B.V.

In November 2017, Horizon Phama Europe B.V. changed name to Chiesi Orphan B.V.

The sponsorship was transferred to Chiesi Farmaceutici S.p.A., Italy, in May 2018.

What is 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.

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

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).

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*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).

What treatments are available?

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.

How is this medicine expected to work?

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).

What is the stage of development of this medicine?

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.

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.

EU/3/10/778: Public summary of opinion on orphan designation: Cysteamine bitartrate (gastroresistant) for the treatment of cystinosis

AdoptedReference Number: EMA/COMP/405606/2010 Rev.1

Key facts

• Active substance:
  Cysteamine bitartrate (gastroresistant) (mercaptamine)
• Medicine name:
  Procysbi
• Intended use:
  Treatment of cystinosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/10/778
• Date of designation:
  20/09/2010
• Sponsor:

  Chiesi Farmaceutici S.p.A.;

Review of designation

During its meeting of 9-11 July 2013, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/778 for Procysbi (mercaptamine¹) as an orphan medicinal product for the treatment of cystinosis. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. As other methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained².

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¹Previously known as cysteamine bitartrate (gastroresistant).
²The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.