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.
In February 2017, Raptor Pharmaceuticals Europe B.V changed name to Horizon Pharma Europe B.V.
- 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).
*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.
|Name||Language||First published||Last updated|
|EU/3/10/778: Public summary of opinion on orphan designation: Cysteamine bitartrate (gastroresistant) for the treatment of cystinosis||(English only)||2010-10-18||2013-10-10|
|Active substance||Cysteamine bitartrate (gastroresistant)|
|Disease/condition||Treatment of cystinosis|
|Date of decision||20/09/2010|
|Orphan decision number||EU/3/10/778|
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.
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.
- Life-threatening or long-term debilitating nature of the condition
The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Procysbi for ‘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’.
This falls within the scope of the product’s designated orphan indication, which is ‘treatment of cystinosis’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Cystinosis remains a condition that is long-term debilitating and life-threatening, because it can lead to kidney failure if left untreated.
- Prevalence of the condition
On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of cystinosis remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 0.1 people in 10,000. This is equivalent to a total of around 5,000 people in the EU.
- Existence of other satisfactory methods of treatment
At the time of the review of the orphan designation, Cystagon (another mercaptamine-containing medicine) was authorised in the EU for the treatment of nephropathic cystinosis. This medicine is available as immediate-release capsules that need to be taken every six hours.
- Significant benefit over existing treatments
The COMP noted that Procysbi is as effective as Cystagon in treating nephropathic cystinosis, and it has a similar safety profile. However, Procysbi is a new gastroresistant formulation of cysteamine that can be given twice a day (every 12 hours), while Cystagon has to be given four times a day (every six hours). The COMP concluded that the claim of a significant benefit of Procysbi over current treatment is justified on the basis that this more convenient formulation makes it easier for patients to stick to their treatment, interfering less with the patient’s daily activities and their sleep. This is therefore considered to make a major contribution to patient care.
Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Procysbi is of significant benefit for patients affected by cystinosis.
Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Procysbi still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community register of orphan medicinal products.
|Name||Language||First published||Last updated|
|Recommendation for maintenance of orphan designation at the time of marketing authorisation: Procysbi (mercaptamine) for the treatment of cystinosis||(English only)||2013-10-10|
Sponsor’s contact details
Horizon Phama Europe B.V.
1043 BW Amsterdam
Tel. + 31 (0) 30 8080 316
Fax. + 31 (0) 30 8080 316
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
- Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
- European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.