EU/3/12/967

Pulmonary arterial hypertension is a condition where there is high blood pressure in the arteries that supply the lungs. In patients with pulmonary arterial hypertension, there is a thickening of the muscles in the walls of the arteries and a narrowing of the arteries in the lungs, making it harder for blood to flow to the lungs.

Pulmonary arterial hypertension is a long-term debilitating and life-threatening condition that shortens patients' life expectancy because it may lead to heart failure and difficulty breathing.

At the time of designation, pulmonary arterial hypertension affected between 1.4 and 2.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of between 71,000 and 137,000 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 (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

Several medicines were authorised for the treatment of pulmonary arterial hypertension in the EU at the time of designation. They included ambrisentan, bosentan, epoprostenol, iloprost, sildenafil, tadalafil and treprostinil. Surgery was also used in some patients to carry out a lung transplant or atrial septostomy (where a small hole is created between the upper two chambers of the heart, the atria).

The sponsor has provided sufficient information to show that sodium nitrite might be of significant benefit for patients with pulmonary arterial hypertension because early studies show that it works in a different way to existing treatments, which may improve the treatment of patients with pulmonary arterial hypertension. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is expected to be available as a solution for inhalation by nebuliser (a small machine that changes a solution into an aerosol that the patient can breathe in). After inhalation, sodium nitrite is converted in the lungs into nitric oxide, which is expected to cause the vessels in the lungs to dilate (widen). This allows blood to flow more easily in the lungs to supply oxygen to the rest of the body and remove carbon dioxide, reducing pulmonary hypertension.

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

At the time of submission of the application for orphan designation, no clinical trials with sodium nitrite in patients with pulmonary arterial hypertension had been started.

At the time of submission, sodium nitrite was not authorised anywhere in the EU for pulmonary arterial hypertension. Orphan designation of sodium nitrite had been granted in the United States of America for pulmonary arterial hypertension.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 January 2012 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 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.