EU/3/16/1626 - orphan designation for treatment of lymphoplasmacytic lymphoma

acalabrutinib

Overview

On 21 March 2016, orphan designation (EU/3/16/1626) was granted by the European Commission to Acerta Pharma, BV, the Netherlands, for acalabrutinib for the treatment of lymphoplasmacytic lymphoma.

What is lymphoplasmacytic lymphoma?

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 the most common type of lymphoplasmacytic lymphoma, called Waldenström's macroglobulinaemia, 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 thick and can lead to disorders 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.

What is the estimated number of patients affected by lymphoplasmacytic lymphoma?

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 isbased 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, the main treatments for diseases such as lymphoplasmacytic lymphoma available in the EU included immunotherapy (medicines that act on the body's immune system), and combinations of immunotherapy with chemotherapy (medicines intended to kill cancer cells). A technique called plasmapheresis was also used to replace the patient's plasma (the liquid part of the blood which contains the IgM paraprotein) with healthy plasma.

The sponsor has provided sufficient information to show that acalabrutinib might be of significant benefit for patients with lymphoplasmacytic lymphoma, because early studies showed that patients whose disease had come back after previous treatment responded to treatment with this medicine. In addition, preliminary results indicate that there might be fewer side effects with acalabrutinib than with the medicine ibrutinib, which is authorised for this condition. These assumptions 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?

Acalabrutinib is expected to work by blocking an enzyme called Bruton's tyrosine kinase (Btk), which is found in B cells. Btk promotes growth and survival of B cells. By blocking Btk, acalabrutinib is expected to slow down the build-up of cancerous B cells in lymphoplasmacytic lymphoma, thereby delaying or stopping the progression of the disease.

The medicine is expected to be taken by mouth.

What is the stage of development of this medicine?

The effects of acalabrutinib have been evaluated in experimental models.

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

At the time of submission, acalabrutinib was not authorised anywhere in the EU for lymphoplasmacytic lymphoma. Orphan designation of acalabrutinib had been granted in the United States for Waldenström macroglobulinaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 February 2016 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.

EU/3/16/1626: Public summary of opinion on orphan designation: Acalabrutinib for the treatment of lymphoplasmacytic lymphoma

AdoptedReference Number: EMA/COMP/150815/2016

Key facts

• Active substance:
  acalabrutinib
• Intended use:
  Treatment of lymphoplasmacytic lymphoma
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1626
• Date of designation:
  21/03/2016
• Sponsor:

  Acerta Pharma BV; Kloosterstraat 9; 5349 AB Oss; The Netherlands; Tel. [phone]; E-mail: [e-mail]

Review of designation

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