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Orphan designation

On 17 March 2003, orphan designation (EU/3/03/139) was granted by the European Commission to Actelion Registration Limited, United Kingdom, for bosentan for the treatment of systemic sclerosis.

What is systemic sclerosis?

Systemic sclerosis involves the abnormal growth of connective tissue, which supports the skin and internal organs. The abnormal growth is due to too much production of a protein called collagen. The disease not only includes the skin, but also involves the tissues around the blood vessels and major organs. Systemic sclerosis is typically broken down into diffuse and limited disease. In diffuse form, the skin becomes thicker over much of the body, such as the upper arms, upper legs, chest, and stomach. Inside the body, the disease can damage key organs such as the heart, lungs, and kidneys. The limited form typically affects the skin only in certain areas: the fingers, hands, face, lower arms, and legs. Many people with limited disease have Raynaud's phenomenon (a condition in which the small blood vessels of the hands and/or feet contract in response to cold or anxiety: they turn white and cold, then blue) for years before the skin starts to become thicker. People with limited disease are more prone to develop hypertension of the heart-lung circulation (pulmonary hypertension) than people with diffuse disease. Due to the thicker skin and the damage to key internal organs, the disease is considered chronically debilitating.

What are the methods of treatment available?

There is no treatment that stops the build-up of collagen. Available treatment is aimed at relieving symptoms and limiting damage. Several products with anti-inflammatory activity (products that limit the reaction of tissues against damage) were authorised for the condition in some countries in the Community at the time of submission of the application for orphan drug designation. Bosentan might be of potential significant benefit for the treatment of systemic sclerosis in particular with regard to efficacy in specific disease related complications. 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*?

According to the information provided by the sponsor, systemic sclerosis was considered to affect about 50,000 people 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 377,000,000 (Eurostat 2001) 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?

Bosentan opposes the effect of a substance called endothelin-1. This substance can cause narrowing of blood vessels and may also play an important role in the disease process of systemic sclerosis. Therefore, bosentan could play an important role in treating major complications of the disease.

What is the stage of development of this medicinal product?

Bosentan has previously received orphan drug designation and has been authorised in the European Union to treat (pulmonary hypertension), which included patients with systemic sclerosis. 

At the time of submission of the application for the current orphan designation, further clinical trials in patients with systemic sclerosis were ongoing.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 7 February 2003 a positive opinion recommending the grant of the above-mentioned designation.

Update: Bosentan (Tracleer) is authorised in the European Union as of 22 March 2007 for the treatment of new digital ulcers in patients with systemic sclerosis and active digital ulcers.

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>Bosentan</p>
Active substanceBosentan
Medicine NameTracleer
Disease/conditionTreatment of systemic sclerosis (scleroderma)
Date of decision17/03/2003
Orphan decision numberEU/3/03/139

Review of designation

Sponsor's contact details:

Actelion Registration Ltd
BSI Building
13th Floor
389 Chiswick High Road
London W4 4AL
United Kingdom
Telephone: +44 20 89 87 33 33
Telefax: +44 20 89 87 33 22

Patients' organisations:

For contact details of patients’ organisations whose activities are targeted at rare diseases see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.