EU/3/20/2283: Orphan designation for the treatment of neonatal encephalopathy

Neonatal encephalopathy refers to brain damage that occurs around the time of birth in babies who are not premature. Oxygen deprivation at birth is one of the most common causes of neonatal encephalopathy. Symptoms include reduced level of consciousness, seizures (fits), difficulty breathing, low muscle tone and poor reflexes.

Neonatal encephalopathy is a long-term debilitating disease due to its effects on mental and physical development, and can be life-threatening in the most severe cases.

At the time of designation, neonatal encephalopathy affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 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).

^*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, babies with neonatal encephalopathy received therapeutic hypothermia, whereby the baby's body is cooled down to a body temperature lower than normal (hypothermia) to reduce extent of damage.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with neonatal encephalopathy because early data suggest that the medicine might benefit patients when used together with therapeutic hypothermia.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Low levels of oxygen in the brain can activate the immune system leading to inflammation and the production of harmful types of oxygen called reactive oxygen species, which can damage brain cells.

The medicine is expected to act on a protein called ‘C1q’, which is part of the body’s immune system. The medicine is also expected to block certain enzymes involved in the production of reactive oxygen species, thereby helping to prevent inflammation and damage and relieve symptoms of the condition.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with neonatal encephalopathy had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of neonatal encephalopathy or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 23 April 2020, 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.