EU/3/03/182

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Orphan designation

On 12 December 2003, orphan designation (EU/3/03/182) was granted by the European Commission to Axovan Europe Ltd., United Kingdom, for clazosentan for the treatment of aneurysmal subarachnoid haemorrhage. The sponsorship was transferred to Actelion Registration Limited, United Kingdom, in January 2005.

What is aneurysmal subarachnoid haemorrhage?

A cerebral aneurysm refers to a blood vessel within the brain that weakens over time and undergoes widening. This usually occurs at the junctions of the large arteries at the base of the brain. As the blood vessel weakens, it begins to bulge out like a balloon. The larger the balloon becomes, the greater the risk it may burst, resulting in haemorrhage (bleeding) into the subarachnoid space (membranous space surrounding the brain) and ensuing spasm (uncontrollable tightening) of the brain blood vessels, leading to further oxygen shortage in the brain cells. This cascade of effects can ultimately impair the brain functions.
Aneurysms in the brain are considered to be acquired, in other words they are not present at birth but develop over a lifetime. However, evidence indicates that genetic factors make some people more likely to develop brain aneurysms. Aneurysmal subarachnoid haemorrhage is chronically debilitating and life-threatening.

What are the methods of treatment available?

Further to surgical intervention, one medicinal product was authorised for the treatment of aneurysmal subarachnoid haemorrhage in the Community at the time of submission of the application for orphan drug designation. Clazosentan might be of potential significant benefit for the treatment of aneurysmal subarachnoid
haemorrhage. This is because it may prevent the complications that are resulting from insufficient blood supply to the brain. This benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

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

According to the information provided by the sponsor, aneurysmal subarachnoid haemorrhage was considered to affect about 48,000 persons in the European Union.

*Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 385,000,000 (Eurostat 2002) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Clazosentan opposes the effect of a substance called endothelin. Endothelin, which is naturally produced by some type of cells of the body, can cause narrowing of blood vessels. Clazosentan blocks the effect of endothelin and the blood vessels can become wider. As such it could prevent and relieve spasm of the blood vessels.

What is the stage of development of this medicinal product?

The effects of clazosentan were evaluated in experimental models. 

At the time of submission of the application for orphan designation, clinical trials in patients with aneurysmal subarachnoid haemorrhage were ongoing.

Clazosentan was not marketed anywhere worldwide for the treatment of aneurysmal subarachnoid haemorrhage or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 November 2003 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments. 

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>5-Methyl-pyridine-2-sulfonic acid{6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridin-4-yl]-pyrimidin-4-yl}-amide sodium salt</p>
Active substance5-Methyl-pyridine-2-sulfonic acid{6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridin-4-yl]-pyrimidin-4-yl}-amide sodium salt
Medicine Name
Disease/conditionTreatment of aneurysmal subarachnoid haemorrhage
Date of decision11/12/2003
OutcomePositive
Orphan decision numberEU/3/03/182

Review of designation

Sponsor’s contact details:

Actelion Registration Limited
BSI Building 13th floor
389 Chiswick High Road
London W44 4AL
United Kingdom
Telephone: +44 20 89 87 33 33
Telefax: +44 20 89 87 33 22