EU/3/14/1264:

Lymphoplasmacytic lymphoma is a cancer of a type of white blood cell called B lymphocytes or B cells. In lymphoplasmacytic lymphoma, the B cells multiply too quickly and live for too long, so there are too many of them in places like the bone marrow, lymph nodes or spleen. The first signs of the disease are usually weakness and tiredness. In many patients with lymphoplasmacytic lymphoma, the abnormal B cells produce too much of a type of blood protein called immunoglobulin-type-M paraprotein (IgM paraprotein), which makes the blood too viscous (thick) and can lead to symptoms such as eye problems, heart failure, haemolytic anaemia (destruction of red blood cells) and effects on the nervous system.

Lymphoplasmacytic lymphoma is a life-threatening and long-term debilitating disease due to damage to the bone marrow and other organs.

At the time of designation, lymphoplasmacytic lymphoma affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 511,100,000 (Eurostat 2014).

At the time of designation, the main treatments for diseases such as lymphoplasmacytic lymphoma available in the EU included immunotherapy (medicines that stimulate the body's own immune system to kill the cancer cells), and combinations of immunotherapy with chemotherapy (cancer medicines intended to kill the cancer cells). Medicines designed to attach to the cancer cells and kill them with radiation (radioimmunotherapy) were also sometimes used.

The sponsor has provided sufficient information to show that ibrutinib might be of significant benefit for patients with lymphoplasmacytic lymphoma, because early studies in patients with lymphoplasmacytic lymphoma that was resistant to or had come back after existing treatments showed that some of these patients responded to ibrutinib. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Ibrutinib is expected to work in patients with lymphoplasmocytic lymphoma by blocking the action of an enzyme known as Bruton's tyrosine kinase (BTK). BTK is important for the growth of B cells, including the abnormal B cells of the cancer. By blocking the action of BTK, it is expected that the medicine will slow the progression of the disease.

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 lymphoplasmacytic lymphoma were ongoing.

At the time of submission, ibrutinib was not authorised anywhere in the EU for lymphoplasmacytic 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 12 March 2014 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.