EU/3/14/1384 - orphan designation for treatment of WHIM syndrome
Orphan
Human
Overview
On 16 December 2014, orphan designation (EU/3/14/1384) was granted by the European Commission to Centre National de la Recherche Scientifique (CNRS), France, for ((E)-1-(4'-chlorophenyl)-3-(4-hydroxy-3-metoxyphenyl)prop-2-en-1-one) for the treatment of WHIM syndrome.
WHIM syndrome is a hereditary condition in which the immune system (the body's natural defences) does not work properly, making patients more susceptible to viral and bacterial infections.
WHIM stands for warts (skin growths), hypogammaglobulinemia (low level of antibodies), infections and myelokathexis (a disorder causing low levels of white blood cells).
Patients with the condition have warts in the hands and feet caused by viral infections, and are at risk of recurrent bacterial infections due to low levels of neutrophils and lymphocytes (types of white blood cells) and of antibodies produced by the white bloods cells to fight infections.
WHIM syndrome is a long-term debilitating and life-threatening condition because of the recurrent infections which increase the risk of developing cancer.
At the time of designation, WHIM syndrome affected approximately 0.002 in 10,000 people in the European Union (EU). This was equivalent to a total of around 100 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 511,100,000 (Eurostat 2014).
At the time of designation, no satisfactory methods were authorised in the EU to treat WHIM syndrome. Patients were given treatment to relieve the symptoms of the condition, including granulocyte-colony stimulating factor which stimulates the bone marrow to produce neutrophils.
Patients with WHIM syndrome have mutations (defects) in the gene for the CXCR4 receptor, which plays a role in the movement of blood cells into and from the bone marrow (where blood cells are produced). Because of these mutations, the CXCR4 receptor is hyperactive. As a result, blood cells, particularly neutrophils, are retained in the bone marrow, leading to low levels of neutrophils in the blood.
This medicine is expected to work by reducing the activity of the CXCR4 receptor. It does this by attaching to and blocking a protein called CXCL12, which usually activate this receptor. By reducing the activity of the CXCR4 receptor, this medicine allows neutrophils to be released from the bone marrow into the blood stream, thereby improving the symptoms of the disease.
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 WHIM syndrome had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for WHIM syndrome 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 November 2014 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
- Intended use
- Treatment of WHIM syndrome
- Orphan designation status
- Positive
- EU designation number
- EU/3/14/1384
- Date of designation
- Sponsor
Centre National de la Recherche Scientifique (CNRS)
3, rue Michel-Ange
Paris Cedex 16
75794
France
Tel. +33 1 44 96 43 42
E-mail: galzi@unistra.fr
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
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.
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
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: