EU/3/17/1865: 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. Symptoms include reduced level of consciousness, seizures (fits), difficulty breathing, low muscle tone and poor reflexes. It is often caused by low levels of oxygen in the blood.

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

At the time of designation, neonatal encephalopathy affected less than 1 in 10,000 people per year 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. 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 515,700,000 (Eurostat 2017).

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 estetrol might be of significant benefit for babies with neonatal encephalopathy because laboratory studies indicate that estetrol could improve symptoms and general well-being of patients affected by the condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Lower levels of oxygen in the brain increase the production of reactive oxygen species which can trigger mechanisms (oxidative stress) that damage cells and ultimately lead to their death.

Results from laboratory studies indicate that estetrol may help protect against oxidative stress. The medicine is therefore expected to help prevent further damage and relieve the baby's symptoms.

The effects of estetrol have been evaluated in experimental models.

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

At the time of submission, estetrol was not authorised anywhere in the EU for neonatal encephalopathy 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 15 March 2017 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.