EU/3/19/2167 - orphan designation for treatment of lymphoplasmacytic lymphoma
Zanubrutinib
OrphanHuman
Overview
On 29 May 2019, orphan designation (EU/3/19/2167) was granted by the European Commission to BeiGene Ireland Limited, Ireland, for zanubrutinib, also known as (BGB-3111), for the treatment of lymphoplasmatic lymphoma.
Please note that this product (marketed as Brukinsa) was withdrawn from the Union Register of orphan medicinal products in October 2021 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation.
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.
At the time of designation, lymphoplasmatic lymphoma affected approximately 1.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 73,000 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 518,400,000 (Eurostat 2019).
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 to treat cancer). A technique called plasmapheresis was also used to remove unwanted IgM paraprotein from the plasma (the liquid part of the blood).
The sponsor has provided sufficient information to show that zanubrutinib might be of significant benefit for patients with lymphoplasmacytic lymphoma. Early studies showed that patients whose disease did not respond to or had come back after previous treatment responded to treatment with this medicine. In addition, indirect comparisons with data from a currently authorised medicine suggest improved outcomes with this medicine. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Zanubrutinib is expected to work in patients with lymphoplasmacytic 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 zanubrutinib have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with zanubrutinib in patients with lymphoplasmatic lymphoma were ongoing.
At the time of submission, zanubrutinib was not authorised anywhere in the EU for the treatment of lymphoplasmatic 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 17 April 2019, 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.
Key facts
- Active substance
- Zanubrutinib
- Intended use
- Treatment of lymphoplasmacytic lymphoma
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/19/2167
- Date of designation
- Sponsor
BeiGene Ireland Limited
Review of designation
The Committee for Orphan Medicinal Products reviewed the orphan designation of product at the time of marketing authorisation.
The sponsor formally requested the withdrawal of the orphan designation prior to the Committee’s final opinion. More information is available in the Brukinsa : Orphan designation withdrawal assessment report (initial authorisation).
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: