EU/3/15/1542: Orphan designation for the treatment of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is a type of blood cancer and the most common form of a group of blood cancers known as non-Hodgkin lymphomas.

Diffuse large B-cell lymphoma 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.

At the time of designation, diffuse large B-cell lymphoma affected approximately 2.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 118,000 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 512,900,000 (Eurostat 2015).

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) usually in combination with other medicines called monoclonal antibodies and 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 medicine might be of significant benefit for patients with diffuse large B-cell lymphoma because early studies in patients suggest that patients whose disease has returned or is not responding to alternative treatments respond to the treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a small piece of DNA that interferes with the BCL2 gene, a gene known to promote cancer cell survival. It does so by targeting and attaching to specific parts of the gene that regulate it. Once attached, it is expected to block the gene's activity resulting in the death of cancer cells.

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the medicine 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 16 July 2015 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.