EU/3/18/2073 - orphan designation for treatment of mucopolysaccharidosis type I
autologous CD34+ haematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LV, encoding for the alpha-L-iduronidase cDNA
OrphanHuman
Overview
On 26 October 2018, orphan designation (EU/3/18/2073) was granted by the European Commission to Fondazione Telethon, Italy, for autologous CD34+ haematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LV, encoding for the alpha-L-iduronidase cDNA for the treatment of mucopolysaccharidosis type I.
The sponsorship was transferred to Orchard Therapeutics (Netherlands) B.V., Netherlands, in January 2020.
Mucopolysaccharidosis type I is an inherited disease caused by the lack of an enzyme called alpha-L-iduronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Since patients with mucopolysaccharidosis type I cannot break down GAGs properly, GAGs build up in various organs in the body and damage them. This can cause a range of symptoms including impaired vision, developmental delay, mental disability, joint stiffness and skeletal problems, breathing difficulties, enlarged liver and heart disease. The condition varies in severity, with the mildest form known as Scheie syndrome and the most severe as Hurler syndrome.
Mucopolysaccharidosis type I is a long-term debilitating and life-threatening disease that leads to multiple disabilities and can result in premature death.
At the time of designation, mucopolysaccharidosis type I affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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, the medicine Aldurazyme (laronidase) was authorised in the EU to treat some of the symptoms of mucopolysaccharidosis type I by replacing the missing enzyme (enzyme replacement therapy). Some patients were treated with haematopoietic stem cell transplantation, a procedure where the patient’s bone marrow is replaced by stem cells from a donor; the stem cells are able to develop into normal blood cells that can produce the missing enzyme.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with mucopolysaccharidosis type I because laboratory studies indicate that it may improve effects on the nervous system, which is not possible with current medicines. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine consists of blood stem cells taken from the patient and treated with a modified virus containing the gene for the missing alpha-L-iduronidase enzyme. The virus carries the gene into the stem cells, enabling them to make blood cells that can produce the enzyme.
When the stem cells are given back to the patient they are expected to begin forming blood cells, including white blood cells called microglia that are found in the brain and spinal cord. These cells will produce the missing enzyme and so can break down GAGs, thereby helping to relieve symptoms of the disease.
The modified virus used to produce this medicine has been designed so that it cannot spread or cause disease in humans.
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 this medicine in patients with mucopolysaccharidosis type I had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for mucopolysaccharidosis type I 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 13 September 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
- autologous CD34+ haematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LV, encoding for the alpha-L-iduronidase cDNA
- Intended use
- Treatment of mucopolysaccharidosis type I
- Orphan designation status
- Positive
- EU designation number
- EU/3/18/2073
- Date of designation
- Sponsor
Orchard Therapeutics (Netherlands) B.V.
Basisweg 10
Noord-Holland
1043 AP Amsterdam
Netherlands
E-mail: regulatory@orchard-tx.com
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 |
|---|---|
| July 2022 | The sponsor's address was updated in July 2022. |
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:
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: