On 15 January 2015, orphan designation (EU/3/14/1418) was granted by the European Commission to Theravectys, France, for a lentiviral vector pseudotyped by the New-Jersey serotype of the vesicular stomatitis virus G protein encoding an antigen derived from the Tax, HBZ, p12I and p30II HTLV-1 proteins for the treatment of adult T-cell leukaemia/lymphoma.
Adult T-cell leukaemia/lymphoma (ATL) is a cancer of a type of white blood cells, called T cells, which play an important role in the immune system (the body's natural defences). It is associated with infection by a virus known as human T-cell leukaemia virus (HTLV-1) though most people infected do not develop the condition.
In patients with ATL there is uncontrolled growth of abnormal, infected T cells in the blood, bone marrow (the tissue inside the large bones in which blood cells are formed) and lymphatic system (the network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream). Over a period of time, the abnormal cells can replace the normal blood and immune cells. Abnormal T cells may also invade other tissues such as the skin. In some patients the disease may develop slowly, whereas in others it takes a more aggressive, rapidly developing form.
In patients with symptomatic disease the condition may be associated with low numbers of normal blood cells, breakdown of bone with resultant high levels of calcium in the blood, and skin lesions (rashes or lumps). The condition is long-term debilitating and potentially life-threatening because the loss of normal immune cells in the blood leaves the patient vulnerable to severe and unusual infections.
At the time of designation, ATL affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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 511,100,000 (Eurostat 2014).
Treatment of ATL depends on the stage and speed of progression. In addition to measures to relieve symptoms, at the time of designation various cancer medicines were authorised in the EU for the treatment of T-cell cancers. Patients whose disease was not progressing rapidly, and who had few or no symptoms, might be monitored until treatment became necessary.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with ATL because initial results from experimental studies suggest that it can trigger the body's own natural defences to attack the abnormal T cells and shrink the cancer. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine contains a version of HIV, the human immunodeficiency virus, which has been modified in various ways so that it can enter cells but cannot reproduce and cannot cause disease. In addition, genes have been inserted into the virus that enable it to produce a protein made up of parts of 4 different proteins produced by HTLV-1, the virus associated with ATL.
When the medicine is given, it causes the cells it enters to produce this protein, which stimulates the immune system to recognise it, and the HTLV-1 proteins that make it up, as 'foreign'. This encourages the immune system to attack and kill cells that are infected with HTLV-1, thus destroying the abnormal T cells and shrinking the cancer.
The medicine is to be given as a booster after a similar medicine containing a slightly different modified virus, in order to increase the stimulation of the immune system and strengthen its effect.
At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.
At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with ATL had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for ATL 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 11 December 2014 recommending the granting of this designation.
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.
THERAVECTYS
1 mail du Pr Georges Mathe
94800 Villejuif
France
Tel. +33 1 43 90 19 20
Fax +33 1 84 16 30 31
E-mail: regulatory@theravectys.com
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: