EU/3/14/1261: Orphan designation for the prevention of bronchopulmonary dysplasia

Bronchopulmonary dysplasia is a lung disease affecting premature babies who have been on prolonged mechanical ventilation (using a machine that supplies oxygen to help with breathing). In premature babies the lungs are immature and do not have enough surfactant, which is a substance lining the lungs and airways that allows them to expand properly. Bronchopulmonary dysplasia is caused by the constant high pressure of the oxygen supplied through mechanical ventilation, which causes inflammation and injury to the lungs and blocks the normal development of the alveoli (air sacs in the lungs). This leads to difficulty breathing and weight loss.

Bronchopulmonary dysplasia is a long-term and life-threatening condition because the underdeveloped lungs may not work properly.

At the time of designation, the number of patients at risk of bronchopulmonary dysplasia was estimated to be between 1 and 3 people in 10,000 in the European Union (EU). This was equivalent to between 51,000 and 153,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of designation, no satisfactory methods of prevention were authorised in the EU for bronchopulmonary dysplasia.

Caffeine citrate is a stimulant of the nervous system and is currently authorised in the EU for the treatment of premature newborns with a breathing disorder called primary apnoea. In the prevention of bronchopulmonary dysplasia, caffeine is expected to act mainly by stimulating the part of the brain that controls breathing, which is thought to help babies breathe on their own and reduce the time spent on mechanical ventilation. In addition, caffeine citrate may also have other effects in the lungs, such as reducing inflammation. These actions are expected to prevent the damage to the lungs in bronchopulmonary dysplasia.

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

At the time of submission of the application for orphan designation, clinical trials with caffeine citrate in patients with bronchopulmonary dysplasia were ongoing.

At the time of submission, caffeine citrate was not authorised anywhere in the EU for bronchopulmonary dysplasia 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 6 February 2014 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.