EU/3/13/1203

On 13 November 2013, orphan designation (EU/3/13/1203) was granted by the European Commission to Janssen-Cilag International N.V., Belgium, for ibrutinib for the treatment of diffuse large B-cell lymphoma.

What is diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma is the most common cancer of the lymphatic system, a network of vessels that transport lymph from tissues through the lymph nodes and into the bloodstream. The cancer affects a type of white blood cell called B lymphocytes, or B cells. In patients with this cancer, the B cells multiply too quickly and live for too long, so there are too many of them in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. Patients with diffuse large B-cell lymphoma may also have fever, tiredness, night sweats or weight loss that have no obvious cause.

Although some people with diffuse large B-cell lymphoma can be cured, it remains a serious and life-threatening disease, particularly when the disease is diagnosed late or has come back after initial treatment.

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

At the time of designation, diffuse large B-cell lymphoma affected approximately 2.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 123,000 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).

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*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 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, several medicines were authorised for the treatment of diffuse large B-cell lymphoma in the EU. The main treatment was chemotherapy (medicines to treat cancer), sometimes in combination with radiotherapy (treatment with radiation). Autologous haematopoietic (blood) stem cell transplantation was also used in patients at risk of the disease coming back after treatment. This is a complex procedure where patients receive their own stem cells to help restore the bone marrow.

The sponsor has provided sufficient information to show that ibrutinib might be of significant benefit for patients with diffuse large B-cell lymphoma because early studies show that it might improve the treatment of patients with this condition, particularly patients whose disease has stopped responding to treatment or has come back after treatment. 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?

Ibrutinib is expected to work in patients with diffuse large B-cell lymphoma by blocking the action of an enzyme known as Bruton’s tyrosine kinase (BTK). BTK is important for the growth and survival of B cells, including the abnormal B cells of the cancer, and their migration to the organs where these cells normally divide. By blocking the action of BTK, it is expected that the medicine will slow the migration of abnormal B cells and induce cell death, thereby slowing the progression of the disease.

What is the stage of development of this medicine?

The effects of ibrutinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with ibrutinib in patients with diffuse large B-cell lymphoma were ongoing.

At the time of submission, ibrutinib was not authorised anywhere in the EU for diffuse large B-cell lymphoma 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 9 October 2013 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.

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