EU/3/03/137: Orphan designation for the treatment of follicular lymphoma

Follicular lymphoma is the consequence of uncontrolled multiplication of lymphocytes, a class of white blood cells involved in immunity and normally present in all organs. Since the lymph nodes are where most lymphocytes reside, this proliferation causes lymph node swelling.

At the time of designation, follicular lymphoma affected approximately 3.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 138,000 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. At the time of designation, this represented a population of 382,800,000 (Eurostat 2003).

At the time of submission of the application for orphan drug designation, several medicinal products were authorised in the European Union for use in follicular lymphoma. The choice of treatment depends in particular on the extension of the disease as well as on the responses to therapies previously prescribed.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that tositumomab might be of potential significant benefit for the treatment of follicular lymphoma in association with iodine 131 radiolabelled tositumomab, particularly in terms of efficacy in advanced cases. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Tositumomab is a monoclonal antibody. This antibody recognises a specific structure on B-cell lymphocytes involved in follicular lymphoma called the CD20 receptor. Activity of the medicinal product is the consequence of the antibody fixation to the lymphocyte.

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

Tositumomab, in association with iodine 131 tositumomab, was granted orphan drug status in the United States of America on 16 May 1994 for the indication of treatment of B-cell non-Hodgkin's lymphoma.

Tositumomab was not marketed anywhere worldwide for follicular lymphoma, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 January 2003 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