EU/3/20/2359 - orphan designation for treatment of frontotemporal dementia
adeno-associated viral vector serotype 9 expressing codon-optimized human GBA gene
OrphanHuman
Overview
On 13 November 2020, orphan designation EU/3/20/2359 was granted by the European Commission to PPD Bulgaria EOOD, Bulgaria, for adeno-associated viral vector serotype 9 expressing codon-optimized human GRN gene (also known as PR006A) for the treatment of frontotemporal dementia.
Frontotemporal dementia is a term for a group of disorders associated with gradual deterioration of brain cells in specific areas of the front and sides of the brain, which control decision-making, behaviour, emotion and language. This leads variously to loss of the ability to control or adjust behaviour, problems with speech and language, and movement disorders.
The exact cause of the disease is unclear, but it is thought to be related to the abnormal build-up and tangling of certain proteins in nerve cells, which are thought to cause the gradual deterioration of brain tissue seen in these patients. Some forms of the disease are associated with changes (mutations) to particular genes.
Frontotemporal dementia is a debilitating disease that can be life threatening because of its damaging effects on the brain.
At the time of designation, frontotemporal dementia affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 114,000 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).
No satisfactory methods of treatment were authorised in the EU for frontotemporal dementia at the time of designation. Patients received symptomatic and supportive treatment.
Five to ten percent patients with frontotemporal dementia have abnormalities in the GRN gene needed to make a protein called progranulin, which has a role in the normal breakdown and recycling of proteins and fats in the body. The medicine contains a virus that has been modified to include a working copy of the gene responsible for the production of progranulin. When the medicine is injected into the brain, the virus is expected to carry the gene into the brain cells, allowing them to produce progranulin. This is expected to improve symptoms of the condition.
The type of virus used in this medicine ('adeno-associated virus'; AAV9) 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 this medicine in patients with frontotemporal dementia had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of frontotemporal dementia. Orphan designation had been granted in the United States for the condition.
In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 8 October 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.
Key facts
- Active substance
- adeno-associated viral vector serotype 9 expressing codon-optimized human GBA gene
- Intended use
- Treatment of frontotemporal dementia
- Orphan designation status
- Positive
- EU designation number
- EU/3/20/2359
- Date of designation
- Sponsor
PPD Bulgaria EOOD
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: