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Orphan designation

On 8 November 2012, orphan designation (EU/3/12/1059) was granted by the European Commission to Nerviano Medical Science Srl, Italy, for milciclib maleate for the treatment of malignant thymoma.

The sponsorship was transferred to Tiziana Life Sciences PLC, United Kingdom, in November 2015.

What is malignant thymoma?

Malignant thymoma is a cancer of the thymus, a gland below the breastbone that is involved in producing infection-fighting cells. Malignant thymoma is most often seen in middle-aged or older people. There may be no symptoms, but some patients have cough, chest pain and difficulty breathing. Up to about half of all patients with malignant thymoma also have myasthenia gravis, a disease causing muscle weakness.

Malignant thymoma is a long-term debilitating and potentially life-threatening illness that is associated with poor long-term survival.

What is the estimated number of patients affected by the condition?

At the time of designation, malignant thymoma affected approximately 0.12 in 10,000 persons in the European Union (EU). This was equivalent to a total of approximately 6,100 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of designation, no satisfactory treatment had been authorised in the EU for patients affected by the condition. Treatments for malignant thymoma may include surgery, radiotherapy (treatment with radiation), and chemotherapy (medicines to treat cancer).

How is this medicine expected to work?

Milciclib maleate blocks the action of specific enzymes called cyclin-dependent kinases (CDKs), which are involved in cell division. In order to become active, CDKs have to attach to proteins called cyclins. Because cancer cells contain many of these cyclins, CDKs become abnormally active leading to the rapid growth of cancer cells. By targeting CDKs and blocking their action, milciclib is expected to interfere with the cell division, eventually killing the cancer cells in malignant thymoma.

Milciclib also blocks a protein called TRKA that is thought to be overactive and stimulate growth of the cancer cells in malignant thymoma. This means that milciclib could have a dual action in controlling the disease.

What is the stage of development of this medicine?

The effects of milciclib maleate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with malignant thymoma were ongoing.

At the time of submission, milciblib maleate was not authorised anywhere in the EU for the treatment of malignant thymoma. Orphan designation of milciclib maleate has been granted in the United States for the treatment of thymic epithelial tumours.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 October 2012 recommending the granting of this designation.

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.

Key facts

Product details for <p>milciclib maleate</p>
Active substancemilciclib maleate
Medicine Name
Disease/conditionTreatment of malignant thymoma
Date of decision08/11/2012
Orphan decision numberEU/3/12/1059

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details

Tiziana Life Sciences PLC
18 South Street
London W1K 1DG
United Kingdom
Tel. +44 (0)20 7493 2853
Fax +44 (0)20 7495 2379

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.