EU/3/19/2149: Orphan designation for the treatment of Huntington’s disease

Huntington’s disease is a hereditary disease that causes brain cells to die. This leads to symptoms such as involuntary jerky movements, behavioural problems and dementia (loss of intellectual function). The disease is usually first noticed between 35 and 45 years of age, and gets worse over time.

Huntington’s disease is caused by defects in the gene responsible for the production of a protein called huntingtin. The gene abnormalities result in an abnormal form of the protein being produced, which causes damage to the cells in specific areas of the brain.

Huntington’s disease is a debilitating and life-threatening condition because it causes severe behavioural and mental problems, a progressive loss of the ability to move and potentially life-threatening complications.

At the time of designation, Huntington’s disease affected approximately 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 62,000 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).

*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 518,400,000 (Eurostat 2019).

At the time of designation, the treatments authorised in the EU for Huntington’s disease were aimed at relieving the symptoms of the disease. In some Member States, haloperidol, pimozide, tetrabenazine and tiapride were authorised for the abnormal involuntary movements that occur in Huntington’s disease. In addition, benzodiazepines were used for anxiety, and antidepressants and lithium to treat depression and mood swings.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with Huntington’s disease. Laboratory data suggest that the medicine may slow down the loss of ability to move, which is not targeted by current treatments.

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

A build-up of cholesterol has been observed in brain cells of patients with Huntington’s disease. This build-up of cholesterol, which can damage brain cells, is thought to be due to a reduction in the enzyme cholesterol 24-hydroxylase that breaks down cholesterol.

The medicine is made of a virus that contains normal copies of the gene that is responsible for the production of the cholesterol 24-hydroxylase enzyme. When injected into the patient’s brain, it is expected that the virus carries the gene into the brain cells, enabling them to produce the enzyme. This is expected to improve symptoms of the disease.

The type of virus used in this medicine (adeno-associated virus) is modified so that it 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 for Huntington’s disease had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for Huntington’s disease 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 21 February 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.