EU/3/17/1919 - orphan designation for treatment of beta thalassaemia intermedia and major

bitopertin

Overview

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in July 2018 on request of the Sponsor.

On 16 October 2017, orphan designation (EU/3/17/1919) was granted by the European Commission to Roche Registration Limited, United Kingdom, for bitopertin for the treatment of beta thalassaemia intermedia and major.

The sponsorship was transferred to Roche Registration GmbH, Germany, in May 2018.

What is beta thalassaemia intermedia and major?

Beta thalassaemia is an inherited disease in which patients are unable to make enough haemoglobin, the iron-rich protein in red blood cells that carries oxygen around the body. Beta thalassaemia major is a severe form of the disease in which patients need frequent blood transfusions. Beta thalassaemia intermedia is a less severe form which may worsen with age. Both types of beta thalassaemia are caused by changes in the gene responsible for producing beta-globin, one of the components of haemoglobin, which result in low levels of haemoglobin in the blood.

Beta thalassaemia intermedia and major are life-long 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.

What is the estimated number of patients affected by the condition?

At the time of designation, beta thalassaemia intermedia and major affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 people¹, 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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¹Disclaimer: 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 515,700,000 (Eurostat 2017).

What treatments are available?

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 'iron overload' - the high iron levels in the body caused by repeated blood transfusions). In some cases, allogeneic haematopoietic stem cell transplantation was used to cure the disease. This is a complex procedure where the bone marrow of the patient is cleared of cells and replaced with healthy bone marrow cells from a matched donor, allowing the patient to produce red blood cells with normal haemoglobin.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with beta thalassaemia intermedia and major because early results from experimental studies suggest it can increase the production of normal haemoglobin and improve symptoms of the condition, which would reduce the need for blood transfusions.This assumption 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?

Normal haemoglobin is made up of both alpha- and beta-globin subunits combined with an iron-containing molecule called 'haem'. Patients with beta thalassaemia intermedia and major cannot make enough beta-globin, and are left with uncombined alpha-globin and haem. Uncombined alpha-globin reduces production of red blood cells by the bone marrow and shortens their life.

Bitopertin blocks a protein called GlyT1 which is needed to make haem. By blocking GlyT1, bitopertin reduces the amount of haem produced, which in turn triggers reduced production of alpha-globin. The damaging effects of alpha-globin on red blood cell production are therefore reduced and the lifespan of red blood cells increased to more normal levels. This is expected to reduce the need for blood transfusions.

What is the stage of development of this medicine?

The effects of bitopertin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with bitopertin in patients with beta thalassaemia intermedia and major had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for beta thalassaemia intermedia and major 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 7 September 2017 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/3/17/1919: Public summary of opinion on orphan designation: Bitopertin for the treatment of beta thalassaemia intermedia and major

Reference Number: EMA/624094/2017

Key facts

• Active substance:
  bitopertin
• Intended use:
  Treatment of beta thalassaemia intermedia and major
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/17/1919
• Date of designation:
  16/10/2017
• Sponsor:

  Roche Registration GmbH;

Review of designation

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