EU/3/05/273

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Orphan designation

On 11 April 2005, orphan designation (EU/3/05/273) was granted by the European Commission to Uppsala Medical Information System AB, Sweden, for ambrisentan for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

The sponsorship was transferred to European Medical Advisory Services Limited, United Kingdom, in August 2005 and subsequently to Glaxo Group Limited, United Kingdom, in September 2006.

What are pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension?

Pulmonary arterial hypertension is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the vessel that leads blood from the heart to the lungs) rises above normal levels. An increase of the number of smooth muscle cells in the walls of small lung arteries (a phenomenon called proliferation) that are remoddeling the vessels, may lead to obstructions in the microcirculation, which will then lead to an increase in the blood pressure.

Chronic thromboembolic pulmonary hypertension is a complication representing less than 1% of all cases of acute pulmonary embolism (the sudden blocking of a lung artery by a clot or foreign material which has been brought to its site by the blood current), which directly leads to pulmonary hypertension. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are chronically debilitating and life-threatening.

What are the methods of treatment available?

Several medicinal products were authorised for the treatment of pulmonary arterial hypertension in the Community at the time of submission of the application for orphan drug designation.

Ambrisentan might be of potential significant benefit for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension because it might act in a different way and thereby improve the long-term outcome of the patients. This benefit will have to be confirmed at the time of marketing authorisation and will be necessary to maintain the orphan status.

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

Based on the information provided by the sponsor and previous knowledge of the Committee, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension was considered to affect less than 2 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 90,000 persons.

* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). 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?

Ambrisentan opposes the effect of a substance called endothelin-1. Endothelin-1 belongs to a group of naturally produced substances, called hormones, released by the cells which are lining the inside surface of the blood vessels. Endothelin-1 is known to be the most powerful substance that can cause narrowing of blood vessels. By blocking the effect of endothelin-1, the diameter of the blood vessels can normalise and this might induce a decrease of the blood pressure.

What is the stage of development of this medicinal product?

At the time of submission of the application for orphan designation, preliminary clinical trials in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension had been performed and more studies were planned.

Ambrisentan was not marketed anywhere worldwide for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension 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 3 March 2005 a positive opinion recommending the grant of the above-mentioned designation.

Update: Ambrisentan (Volibris) is authorised in the European Union as of 21 April 2008 for the treatment of pulmonary arterial hypertension (PAH).

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>Ambrisentan</p>
Active substanceAmbrisentan
Medicine NameVolibris
Disease/conditionTreatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
Date of decision11/04/2005
OutcomePositive
Orphan decision numberEU/3/05/273

Review of designation

Sponsor’s contact details:

Glaxo Group Limited
Glaxo Wellcome House
Berkely Avenue
Greenford
Middlesex UB6 0NN
United Kingdom
Telephone: +44 20 84 22 34 34
Telefax: +44 20 84 23 44 01

Patients associations’ contact points:

Association HTAPFrance
31 rue Jacques Cellier 
F-51100 Reims
France 
Telephone : +33 3 26 36 93 32 
E-mail : secretariat@htapfrance.com

Pulmonale Hypertonie 
Kriegsstraße 25 
D-76133 Karlsruhe
Germany 
Telephone: +49 721 352 83 81 
Telefax: +49 721 352 88 80 
E-mail: info@phev.de

Pulmonary Hypertension Association 
PO Box 2760 
Lewes Sussex BN8 4WA
United Kingdom 
Telephone: +44 800 389 81 56 
Telefax: (44-701) 071 57 23 
E-mail: pha_uk@hotmail.com