EU/3/18/2036 - orphan designation for treatment of cystinuria
L-cystine bis(N-methylpiperazide)
OrphanHuman
Overview
On 27 June 2018, orphan designation (EU/3/18/2036) was granted by the European Commission to PharmaKrysto Ltd, United Kingdom, for L-cystine bis(N'-methylpiperazide) (also known as L-CDNMP) for the treatment of cystinuria.
The sponsorship was transferred to Regulis Consulting Europe Limited, Ireland, in March 2019.
The sponsorship was transferred to Regulis Consulting Europe Limited, Ireland, in March 2019 and subsequently to YES Pharmaceutical Development Services GmbH, Germany, in April 2021.
Cystinuria is an inherited condition caused by a mutation (change) in the genes that produce the protein rBAT, which transports the amino acid cystine out of the urine and gut. Because the mutation means that rBAT does not work properly, people with the condition develop high concentrations of cystine in their urine. As cystine is poorly soluble, it crystallises in the urine inside the kidney, forming kidney stones that can damage the kidneys and block passage of urine. The condition is long-term debilitating due to the pain, bleeding, obstruction and risk of infection and kidney damage caused by the stones.
At the time of designation, cystinuria affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 26,000 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 517,400,000 (Eurostat 2018).
At the time of designation, patients were managed with increased fluid intake, restriction of sodium and protein in the diet, and with substances such as potassium citrate to make the urine more alkaline and so improve the amount of cystine it can dissolve, reducing the risk of stones. In some EU countries the medicines penicillamine and tiopronin were authorised for treatment in patients who could not be managed with other measures.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with cystinuria because it works in a different way to available treatments and laboratory studies suggest that it can reduce formation of cystine kidney stones more effectively. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Crystals of cystine grow because cystine molecules can lock together in a regular pattern. This medicine is able to attach to the developing crystal and disrupt this pattern, preventing the crystal from forming. When taken by mouth the medicine appears in the urine, and is expected to stop crystal formation and development of stones in the kidney, thus preventing the symptoms and complications of the condition.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with cystinuria had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for cystinuria 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 24 May 2018 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.
Key facts
- Active substance
- L-cystine bis(N-methylpiperazide)
- Intended use
- Treatment of cystinuria
- Orphan designation status
- Positive
- EU designation number
- EU/3/18/2036
- Date of designation
- Sponsor
YES Pharmaceutical Development Services GmbH
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
Update history
| Date | Update |
|---|---|
| August 2023 | The sponsor’s address was updated in August 2023. |
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: