EU/3/19/2170 - orphan designation for treatment of beta thalassaemia intermedia and major

2-(2-{[2-(1H-benzimidazol-2-yl)ethyl]amino}ethyl)-N-[(3-fluoropyridine-2-yl)methyl]-1,3-oxazole-4-carboxamide trihydrochloride

Overview

On 28 June 2019, orphan designation EU/3/19/2170 was granted by the European Commission to Vifor France S.A., France, for 2-(2-{[2-(1H-benzimidazol-2-yl)ethyl]amino}ethyl)-N-[(3-fluoropyridin-2-yl)methyl]-1,3-oxazole-4-carboxamide trihydrochloride (also known as VIT-2763) 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 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 approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 52,000 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).

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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 518,400,000 (Eurostat 2019).

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. This is because results from laboratory studies suggest it can reduce anaemia, a symptom that existing treatments do not address. 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?

The medicine blocks a protein, ferroportin, which transports iron from inside the cells into the bloodstream. This is expected to reduce iron levels in the blood and to decrease the damaging effect of high blood iron levels on the formation of red blood cells, thus improving anaemia and the symptoms of the condition.

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 the treatment of beta-thalassaemia intermedia and major 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 23 May 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.

EU/3/19/2170: Public summary of opinion on orphan designation: 2-(2-{[2-(1H-benzimidazol-2-yl)ethyl]amino}ethyl)-N-[(3-fluoropyridin-2-yl)methyl]-1,3-oxazole-4-carboxamide trihydrochloride for the treatment of beta-thalassaemia intermedia and major

Adopted Reference Number: EMADOC-628903358-1042

Key facts

• Active substance:
  2-(2-{[2-(1H-benzimidazol-2-yl)ethyl]amino}ethyl)-N-[(3-fluoropyridine-2-yl)methyl]-1,3-oxazole-4-carboxamide trihydrochloride
• Intended use:
  Treatment of beta thalassaemia intermedia and major
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2170
• Date of designation:
  28/06/2019
• Sponsor:

  Vifor France S.A.; Tour Franklin La Defense 8; 100-101 Terrasse Boieldieu; Puteaux; 92042 Paris La Defense Cedex; France ; Tel. [phone] (Switzerland); E-mail: [e-mail]