On 29 July 2014, orphan designation (EU/3/14/1300) was granted by the European Commission to IDEA Innovative Drug European Associates Limited, the United Kingdom, for recombinant fusion protein consisting of a modified form of the extracellular domain of human activin receptor IIB linked to the human IgG1 Fc domain for the treatment of beta thalassaemia intermedia and major.
This medicine is now known as luspatercept.
The sponsorship was transferred to Celgene Europe Limited, United Kingdom, in February 2015. The sponsorship was transferred to Celgene Europe B.V., The Netherlands, in September 2018.
Recombinant fusion protein consisting of a modified form of the extracellular domain of human activin receptor IIB linked to the human IgG1 Fc domain for treatment of beta thalassaemia intermedia and major has been authorised in the EU as Reblozyl since 25 June 2020.
The sponsorship was transferred to Bristol-Myers Squibb Pharma EEIG, Ireland in February 2021.
The medicinal product has been authorised in the EU as Reblozyl since 25 June 2020.
Beta thalassaemia is an inherited disease in which patients are unable to make enough haemoglobin, the protein found in red blood cells that carry oxygen around the body. Beta thalassaemia major is a severe form of the disease in which patients need frequent blood transfusions, while beta thalassaemia intermedia is a less severe form, which may worsen with age.
Both beta thalassaemia intermedia and major are caused by defects in the gene responsible for the production of beta-globin, one of the components of haemoglobin, which result in low or no production of beta-globin.
Beta thalassaemia intermedia and major are long-lasting debilitating diseases. They may be life threatening because of severe anaemia (low red blood cell count due to lack of haemoglobin), the need for repeated blood transfusions and the risk of complications associated with them.
At the time of designation, beta thalassaemia major and minor affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).
At the time of designation, the main treatments for beta thalassaemia intermedia and major were blood transfusions and the use of iron chelators (medicines for reducing the high iron levels in the body caused by repeated blood transfusions). In some cases, bone-marrow transplantation was used to cure the disease. This is a complex procedure in which the bone marrow of the patient is destroyed and replaced with bone marrow from a matched donor, to allow the patient to produce red blood cells with normal levels of haemoglobin.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with beta thalassaemia intermedia or major because early studies show that it may improve anaemia, an aspect of the condition that is not targeted by currently authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
In patients with beta-thalassemia, the bone marrow has too many precursor red blood cells that fail to develop into mature red blood cells.
This medicine is an engineered protein that has been designed to attach to certain proteins in the body which slow down (or inhibit) the maturation of red blood cells. By attaching to these 'inhibitory' proteins, it is expected to trap them so they do not have their normal effect on the red blood cells. As a result, production of red blood cells is increased. This is expected to improve the symptoms of patients with beta thalassaemia intermedia and major.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with beta thalassaemia intermedia and major were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for beta thalassaemia intermedia and major. Orphan designation of the medicine had been granted in the United States for beta thalassaemia.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 June 2014 recommending the granting of this designation.
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.
Bristol-Myers Squibb Pharma EEIG
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Tel. +353 1 483 3857
E-mail: medical.information@bms.com
The Committee for Orphan Medicinal Products reviewed the orphan designation of Reblozyl at the time of change to the terms of the marketing authorisation, and confirmed that the orphan designation should be maintained:Reblozyl : Orphan maintenance assessment report (post authorisation)
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: