EU/3/20/2296: Orphan designation for the treatment of marginal zone lymphoma

Marginal zone lymphoma is a group of slow-growing cancers of blood cells called B lymphocytes or B cells. In most cases it grows outside the lymph nodes (glands throughout the body that are part of the body’s natural defences), in places such as the stomach, salivary gland, thyroid, eyes, lungs, spleen and blood. Symptoms of the disease depend on where the lymphoma develops.

Marginal zone lymphoma is a life-threatening and long-term debilitating disease due to its effects on the spleen, lymph nodes and bone marrow, as well as the increased risk of infection.

At the time of designation, marginal zone lymphoma affected approximately 1.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 88,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, the main treatments for marginal zone lymphoma available in the EU included chemotherapy (cancer medicines), immunotherapy (using the body’s own immune system to kill cancer cells) with the medicine rituximab, radiotherapy (treatment with radiation) and surgery to remove affected lymph nodes. In some patients, marginal zone lymphoma affecting the stomach is associated with infection by the bacterium Helicobacter pylori, and treatment with antibiotics is used.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with marginal zone lymphoma because the cancer responded to the medicine in some patients whose disease had not responded or had come back after other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is a form of immunotherapy. It contains the patient’s own T cells (a type of white blood cell) that have been modified in the laboratory to make a protein called chimeric antigen receptor (CAR). CAR can attach to another protein called CD19 found on the cancer cells.

When the medicine is given to the patient, the modified T cells are expected to attach to and kill the cancer cells, thereby helping to clear the cancer from the body.

The effects of axicabtagene ciloleucel have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with axicabtagene ciloleucel in patients with marginal zone lymphoma were ongoing.

At the time of submission, axicabtagene ciloleucel was authorised in the EU for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, under the name Yescarta. The medicine was not authorised anywhere in the EU for the treatment of marginal zone lymphoma or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 May 2020, 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.