EU/3/04/234 - orphan designation for treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

sitaxentan sodium

Overview

Please note that this product was withdrawn from the Community register of designated orphan medicinal products in March 2013 on request of the sponsor.

On 21 October 2004, orphan designation (EU/3/04/234) was granted by the European Commission to PPD Global Ltd, UK, for sitaxentan sodium for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

The sponsorship was transferred to Encysive (UK) Ltd, United Kingdom, in July 2005 and to Pfizer Limited, United Kingdom, in September 2010.

Sitaxentan sodium was authorised in the EU as Thelin on 10 August 2006.

The marketing authorisation was withdrawn on 10 December 2010.

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 blood vessel that leads 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 remodelling 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 is the estimated number of patients affected by the condition?

At the time of designation, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 93,000 people*, and is below the threshold 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004.

What treatments are 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.

Sitaxentan sodium 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. The benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

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

What is the stage of development of this medicine?

The effects of sitaxentan sodium have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension were ongoing.

Sitaxentan sodium was not marketed anywhere worldwide for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, at the time of submission. Orphan designation has been granted for sitaxentan in the United States for the same condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2004 recommending the granting of this designation.

Update: Sitaxentan sodium (Thelin) was authorised in the EU on 10 August 2006 for the treatment of patients with pulmonary arterial hypertension classified as World Health Organization functional class III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease.

This medicine has been been withdrawn from use in the EU since 2 March 2013.

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/3/04/234: Public summary of positive opinion for orphan designation of sitaxentan sodium for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

AdoptedReference Number: EMEA/COMP/69492/04 Rev. 3

Key facts

• Active substance:
  sitaxentan sodium
• Medicine name:
  Thelin
• Intended use:
  Treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/04/234
• Date of designation:
  21/10/2004
• Sponsor:

  Pfizer Limited; Ramsgate Road; Sandwich; Kent; CT13 0NJ; United Kingdom; Tel. [phone]; Fax [phone]; E-mail: [e-mail]