EU/3/04/216: Orphan designation for the respiratory distress syndrome in premature neonates of less than 32 weeks of gestational age

Respiratory distress syndrome (RDS) is a lung disorder that causes increasing difficulty in breathing. It may occur in adults (adult respiratory distress syndrome) or in newborn children, when it is also known as hyaline membrane disease. RDS in premature, low birth weight infants is characterised by the onset of difficulty in breathing within minutes to a few hours after birth. The condition is associated with the presence of deposits of a dense membrane (called hyaline membrane) in the air sacs (alveoli) of the lung. RDS is a life-threatening condition.

At the time of designation, the number of premature neonates of less than 32 weeks of gestational age at risk of respiratory distress syndrome was estimated to be approximately 1.1 people in 10,000 in the European Union (EU) *. This is equivalent to a total of around 51,000 people, which 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 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

Several surfactant products (see definition below) were authorised for prevention of the condition in the Community at the time of submission of the application for orphan drug designation. Other methods of prevention include the administration of steroidal medication to the expectant mother to accelerate lung development in the unborn child.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that Surfaxin might be of potential significant benefit for the prevention of RDS in premature neonates. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Surfaxin is a surfactant agent. Lung surfactant is a protein and fat complex that coat the alveoli of the lung, and keep them open. This ensures a stable alveoli surface for oxygen passage.

Surfactant substances are naturally produced in lungs. In premature neonates the lungs have not fully matured and there may be a deficiency of natural surfactant. Surfaxin is intended to compensate for the lack of natural surfactant in infants with RDS and thus aims to improve the lung function.

The effects of sinapultide, dipalmitoylphosphatidylcholine, palmitoyl-oleoyl phosphatidylglycerol and palmitic acid were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in pemature neonates at risk of developing RDS were completed

This medicinal product was not marketed anywhere worldwide for RDS at the time of submission. Orphan designation of Surfaxin has previously been granted in the European Union for treatment of meconium aspiration syndrome (EU/3/01/054) and treatment of acute lung injury (EU/3/01/079).

In the United States orphan drug status has been granted for: treatment of acute respiratory distress syndrome in adults, treatment of respiratory distress syndrome in premature infants, and treatment of meconium aspiration syndrome in newborn infants.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 16 June 2004 a positive opinion recommending the grant of the above-mentioned 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 Community) 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.