EU/3/18/2081 - orphan designation for treatment of ATTR amyloidosis
3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid
OrphanHuman
Overview
Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2024 on request of the Sponsor.
On 19 November 2018, orphan designation (EU/3/18/2081) was granted by the European Commission to Pharma Gateway AB, Sweden, for 3-(3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid (also known as AG10) for the treatment of ATTR amyloidosis.
The sponsorship was transferred to Bridge Bio Europe B.V., Netherlands, in November 2021.
ATTR amyloidosis or transthyretin-mediated amyloidosis belongs to a group of diseases called systemic amyloidosis in which deposits of proteins (called amyloids) accumulate and cause damage in body organs. In ATTR amyloidosis, the amyloids are made up of an abnormal form of transthyretin, a protein produced in the liver that transports various substances in the blood.
In patients with ATTR amyloidosis, the amyloids accumulate mainly in the heart and the nervous system. Patient with this condition usually have heart problems and symptoms such as muscle weakness in the limbs and, at later stages, inability to walk, problems affecting the stomach and the gut (leading to malnutrition), and bladder dysfunction.
ATTR amyloidosis is a long-term debilitating disease due to the progressive worsening of nervous system symptoms. It is also life threatening because amyloid deposits in the heart can cause fatal heart conditions.
At the time of designation, ATTR amyloidosis affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 517,400,000 (Eurostat 2018).
At the time of designation, the medicines Vyndaqel (tafamidis), Tegsedi (inotersen) and Onpattro (patirisan) were authorised in the EU to treat ATTR amyloidosis in patients with the early stages of nerve disease. The only other treatment option was liver transplantation.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with ATTR amyloidosis because early results suggest that it can be of value in patients with heart problems, whereas existing treatments are authorised for patients with symptoms affecting the nervous system. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
This medicine acts as a stabilizer of transthyretin, the protein that makes up the amyloids in patients with ATTR amyloidosis. After being taken by mouth it attaches to transthyretin in the blood, which prevents the abnormal protein from breaking up and forming amyloids. This is expected to slow down the progression of the disease.
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 ATTR amyloidosis were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for ATTR amyloidosis 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 11 October 2018 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
- 3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid
- Intended use
- Treatment of ATTR amyloidosis
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/18/2081
- Date of designation
- Sponsor
Bridge Bio Europe B.V.
Herikerbergweg 238
1101 CM Amsterdam
Noord-Holland
Netherlands
Email: info@bridgebio.com
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
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:
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: