EU/3/19/2240: Orphan designation for the treatment of non-traumatic subarachnoid haemorrhage

Non-traumatic subarachnoid haemorrhage is bleeding into the subarachnoid space (the space between two membranes that surround the brain). The bleeding is not due to an injury to the head but is usually caused by the bursting of a weakened blood-vessel wall in the brain (a cerebral aneurysm). It is a form of stroke, and the bleeding increases pressure on the brain and damages surrounding brain tissue. In addition, blood vessels near the site of the aneurysm go into spasm (vasospasm) reducing the supply of oxygen and essential nutrients to brain cells from the blood. Patients may develop seizures (fits) and other complications including heart problems.

Non-traumatic subarachnoid haemorrhage is life threatening and debilitating because of brain damage, impairment of brain functions and heart problems.

At the time of designation, non-traumatic subarachnoid haemorrhage affected approximately 1 in 10,000 people per year in the European Union (EU). This was equivalent to a total of around 52,000 people per year*, 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 (European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

Treatment of subarachnoid haemorrhage involves surgery or a procedure using a catheter to close or block off the bleeding blood vessel. At the time of designation, nimodipine, a medicine that relaxes blood vessels and lowers blood pressure, was authorised in the EU for the prevention and treatment of complications due to vasospasm following subarachnoid haemorrhage.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with non-traumatic subarachnoid haemorrhage because early results suggest it may reduce the risk of vasospasm better than nimodipine. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Nicardipine is a medicine known as a calcium-channel blocker that has been used in the EU for many years to treat angina (chest pains caused by reduced blood flow to the heart) and high blood pressure. Like the related substance nimodipine it relaxes and widens blood vessels, reducing blood pressure and improving the flow of blood. In this medicine it has been incorporated into an implant that steadily releases nicardipine. When this is implanted in the brain during surgery to repair the bleeding blood vessel, it supplies nicardipine just to the area where it is needed, relaxing the surrounding blood vessels and preventing them from going into vasospasm.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with non-traumatic subarachnoid haemorrhage were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of non-traumatic subarachnoid haemorrhage 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 5 December 2019, 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.