EU/3/14/1402 - orphan designation for treatment of beta thalassaemia intermedia and major

Benserazide hydrochloride

Overview

On 16 December 2014, orphan designation (EU/3/14/1402) was granted by the European Commission to Isabelle Ramirez, Germany, for benserazide hydrochloride for the treatment of beta thalassaemia intermedia and major.

What is beta thalassaemia intermedia and major?

Beta thalassaemia is an inherited disease in which patients are unable to make enough beta-globin, one of the components of adult haemoglobin, which is the protein found in red blood cells that carries oxygen around the body in adults. 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, which result in low or no production of adult haemoglobin. In the more severe forms of the disease symptoms usually appear by two years of age, when the production of fetal haemoglobin (the main type of haemoglobin found in unborn children) is deactivated and the production of adult haemoglobin is activated.

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.

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

At the time of designation, beta thalassaemia intermedia and major 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 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 511,100,000 (Eurostat 2014).

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 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 the condition because early studies show that it promotes the production of fetal haemoglobin which is expected to replace the missing adult haemoglobin, reducing 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?

At birth, the gene that guides the production of fetal haemoglobin is 'switched off', and the production of adult haemoglobin is activated. However, patients with beta thalassaemia are unable to produce functional adult haemoglobin, because of their inability to produce beta-globin. Production of fetal haemoglobin is not compromised in these patients because fetal haemoglobin does not contain beta-globin sub-units, but gamma-globulin.

Benserazide hydrochloride is expected to act by keeping the gene for fetal haemoglobin 'switched on'. Fetal haemoglobin is expected to replace the missing haemoglobin in patients with beta thalassaemia, thereby reducing the need for blood transfusions.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine 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.

At the time of submission, the medicine in combination with levodopa was authorised in several EU Member States for the treatment of Parkinson's disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 November 2014 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/3/14/1402: Public summary of opinion on orphan designation: Benserazide hydrochloride for the treatment of beta thalassaemia intermedia and major

AdoptedReference Number: EMA/COMP/736552/2014

Key facts

• Active substance:
  Benserazide hydrochloride
• Intended use:
  Treatment of beta thalassaemia intermedia and major
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/14/1402
• Date of designation:
  16/12/2014
• Sponsor:

  Isabelle Ramirez; Steinstrasse 54; Munich; D-81667; Germany; Tel. [phone]; Fax [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.