EU/3/10/815: Orphan designation for the treatment of postcardiotomy right ventricular failure

Right ventricular failure occurs when the right part of the heart stops working properly. The right part of the heart pumps blood that has come from all over the body towards the lungs. Patients with right ventricular failure may have hypoxaemia (poor blood oxygenation), low blood pressure, poor blood circulation and accumulation of fluid in parts of the body such as legs and feet which may become swollen. Postcardiotomy right ventricular failure is the term to describe this condition when it occurs in patients who have recently had heart surgery.

Postcardiotomy right ventricular failure is a life-threatening condition with a high mortality rate.

At the time of designation, postcardiotomy right ventricular failure affected less than 1 person in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 51,000 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).

*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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of postcardiotomy right ventricular failure. Patients were treated with standard methods to improve blood circulation.

Sildenafil is a medicine that has been used for a number of years to improve blood flow in patients with erectile dysfunction (impotence) and with pulmonary arterial hypertension (high blood pressure in the artery that leads from the heart to the lungs). Sildenafil works by blocking an enzyme called phosphodiesterase type 5. When this enzyme is blocked, a substance called 'cyclic guanine monophosphate' (cGMP) cannot be broken down, so that it remains in the vessels where it causes the relaxation and widening of the blood vessels. In postcardiotomy right ventricular failure, sildenafil is expected to work by widening the blood vessels of the lungs thus making the pumping action of the right side of the heart easier.

The effects of sildenafil citrate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with sildenafil in patients with postcardiotomy right ventricular failure had been started.

At the time of submission, sildenafil was not authorised anywhere in the EU for postcardiotomy right ventricular failure or designated as an 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 9 September 2010 recommending the granting of this designation.

• 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 European Union) 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.