EU/3/10/780 - orphan designation for treatment of chronic lymphocytic leukaemia

Forodesine

Overview

On 20 September 2010, orphan designation (EU/3/10/780) was granted by the European Commission to Mundipharma Research Limited, United Kingdom, for forodesine for the treatment of chronic lymphocytic leukaemia.

The sponsorship was transferred to Mundipharma Corporation (Ireland) Limited, Ireland, in April 2019.

What is chronic lymphocytic leukaemia?

Chronic lymphocytic leukaemia (CLL) is cancer of a type of white blood cell called B lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so that there are too many of them circulating in the blood. The cancerous lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time, the abnormal cells replace the normal white blood cells, red blood cells and platelets (components that help the blood to clot) in the bone marrow (the spongy tissue inside the large bones in the body).

CLL is the most common type of leukaemia and mainly affects older people. It is rare in people under the age of 40 years. CLL is a long-term debilitating and life-threatening disease because some patients develop severe infections.

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

At the time of designation, CLL affected approximately 3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 152,000 people, and is below the threshold 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. This represents a population of 506,500,000 (Eurostat 2010).

What treatments are available?

Treatment for CLL is complex and depends on a number of factors, including the extent of the disease, whether it has been treated before, and the patient's age, symptoms and general state of health. Patients whose CLL is not causing any symptoms or is only getting worse very slowly may not need treatment. Treatment for CLL is only started if symptoms become troublesome. At the time of designation, the main treatment for CLL was chemotherapy (medicines to treat cancer).

The sponsor has provided sufficient information to show that forodesine might be of significant benefit for patients with CLL because it works in a different way to existing treatments and because early studies indicate that it might improve the treatment of patients with this condition, particularly patients who do not respond to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Forodesine is expected to work by blocking an enzyme called 'purine nucleoside phosphorylase' (PNP). Blocking the activity of this enzyme causes a substance called dGTP to build up in some types of cell, including B lymphocytes. dGTP is toxic to cells if it is present in large amounts. As a result, forodesine is expected to help slow down or stop the uncontrolled division of B lymphocytes in CLL.

What is the stage of development of this medicine?

The effects of forodesine have been evaluated in experimental models.

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

At the time of submission, forodesine was not authorised anywhere in the EU for CLL. Orphan designation of forodesine hydrochloride had been granted in the United Sates of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2010 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.

EU/3/10/780: Public summary of opinion on orphan designation: Forodesine for the treatment of chronic lymphocytic leukaemia

Adopted Reference Number: EMA/COMP/397978/2010

Key facts

• Active substance:
  Forodesine
• Intended use:
  Treatment of chronic lymphocytic leukaemia
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/10/780
• Date of designation:
  20/09/2010
• Sponsor:

  Mundipharma Corporation (Ireland) Limited; Millbank House; 18 Arkle Road; Sandyford Industrial Estate; Dublin 18; Co. Dublin; D18 C6R3; Ireland; Tel. [phone]; E-mail: [e-mail]

Review of designation

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