EU/3/00/014: Orphan designation for the treatment of primary and of the following forms of secondary pulmonary hypertension…

Primary pulmonary hypertension (PPH) is a disease of unknown cause. The condition seriously restricts physical capacity, and in turn, the patient's quality of life. Its symptoms include shortness of breath (that occurs or gets worse with exercise), chest pain, and syncope (fainting, a sudden, temporary, loss of consciousness generally caused by insufficient oxygen in the brain).

At the time of designation, primary and certain forms of secondary pulmonary hypertension affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 83,000 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).

*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. At the time of designation, this represented a population of 375,500,000 (Eurostat 2000).

Current medications for the management of the condition include calcium-channel blockers (drugs that stop calcium entering the cells) and vasodilators (drugs that widen blood vessels).

Satisfactory argumentation has been submitted by the sponsor to justify assumption that iloprost might be of potential significant benefit for the treatment of the condition because it could cause fewer side effects than the current treatment and improve the quality of life of the patients. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

According to the sponsor, iloprost acts by stopping thrombosis (the formation of a blood clot, thrombus inside a blood vessel). Furthermore, it is expected to protect endothelial cells that line the inner wall of blood vessels from narrowing (vasoconstriction) and also widen constricted blood vessels. The effects are thought to improve the symptoms of primary and certain forms of secondary pulmonary hypertension.

The effects of iloprost have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with primary and secondary pulmonary hypertension forms of interest were ongoing.

At the time of submission, iloprost was not authorised anywhere in the world for the treatment of primary and of the following forms of secondary pulmonary hypertension: connective-tissue-disease pulmonary hypertension, drug-induced pulmonary hypertension, portopulmonary hypertension, pulmonary hypertension associated with congenital heart disease and chronic thromboembolic pulmonary hypertension or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 27 October 2000 recommending the granting of this designation.

Update: Iloprost (Ventavis) was authorised in the EU on 16 September 2003 for the treatment of patients with primary pulmonary hypertension, classified as New York Heart Association functional class III, to improve exercise capacity and symptoms.

• 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.