EU/3/15/1504: Orphan designation for the treatment of follicular lymphoma

Follicular lymphoma is a cancer of a type of white blood cell called B lymphocytes or B cells. In follicular lymphoma, 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, caused by an enlarged lymph node. Patients may also have fever, weight loss, tiredness and night sweats.

Follicular lymphoma is usually diagnosed in people aged over 50 years. It is a life-threatening and long-term debilitating disease due to organ damage and the cancer coming back.

At the time of designation, follicular 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).

*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, the main treatments for follicular lymphoma available in the EU included chemotherapy (medicines to treat cancer) combined with immunotherapy (medicines that stimulate the body's own immune system to kill the cancer cells). The medicines bendamustine, ibritumomab tiuxetan, interferon alfa 2b and rituximab were specifically authorised for the treatment of follicular lymphoma.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with follicular lymphoma because early studies show that patients whose disease has come back after treatment might respond to treatment with obinutuzumab. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Obinutuzumab is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Obinutuzumab has been designed to attach to a protein called CD20, which is present on the surface of all B cells, including the large number of cancerous B cells that are present in the lymph nodes of patients with follicular lymphoma. When obinutuzumab attaches to CD20, it is expected to cause the death of the cancerous B cells, slowing down the growth of the cancer.

Obinutuzumab is currently authorised in the EU as Gazyvaro for use in combination with chlorambucil (another cancer medicine) to treat patients with previously untreated chronic lymphocytic leukaemia.

The effects of obinutuzumab have been evaluated in experimental models.

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

At the time of submission, obinutuzumab was not authorised anywhere in the EU for follicular lymphoma. Orphan designation of obinutuzumab has been granted in the United States for follicular lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 May 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.