EU/3/20/2287: Orphan designation for the treatment of Canavan disease

Canavan disease is an inherited disease that affects the normal functioning of the nerves, the brain and spinal cord.

The disease is caused by a mutation (change) in the gene responsible for producing an enzyme called ASPA, which is involved in maintaining myelin, a protective sheath around nerve cells that also speeds up the transmission of impulses (messages) along nerves. Because of these mutations, ASPA does not work properly leading to problems with the development of the brain and spinal cord and messaging between nerves throughout the body.

The disease usually starts at birth and affected infants do not develop normally and have an unusually large head size. As the disease progresses, patients develop loss of muscle strength, damage to the optic nerve and stiffening of muscles. Patients often have swallowing difficulties, sleep disturbances, inability to move voluntarily and experience seizures (fits). 

Canavan disease is long-term debilitating and life threatening with a life expectancy of less than 10 years for the severe form of the disease.

At the time of designation, Canavan disease affected approximately 0.04 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,000 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, no satisfactory methods were authorised in the EU for the treatment of Canavan disease. Patients received supportive treatment to protect airways and provide nutrition and hydration. Patients also received treatment to temporarily relieve the symptoms of the disease, such as medicines to treat epilepsy and spasticity.

This medicine is made of a virus that contains a normal copy of the gene for ASPA. When given to the patient, the virus is expected to carry the gene into the nerve cells in the brain, enabling them to produce a working ASPA, thus reducing the damage to myelin and maintaining their normal functioning. 

The virus used in this medicine ('adeno-associated virus') does not cause disease in humans. 

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Canavan disease 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.