On 29 April 2014, orphan designation (EU/3/14/1267) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for synthetic double-stranded siRNA oligonucleotide directed against transthyretin mRNA and covalently linked to a ligand containing three N-acetylgalactosamine residues for the treatment of ATTR amyloidosis.
The sponsorship was transferred to Alnylam UK Limited, United Kingdom, in November 2014.
Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in April 2017 on request of the Sponsor.
ATTR 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 transthyretin, a protein produced in the liver that transports various substances in the blood.
In patients with ATTR amyloidosis, transthyretin deposits accumulate mainly in the heart and the nervous system causing 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 isbased 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. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).
At the time of designation, the only medicine authorised in the EU to treat ATTR amyloidosis was Vyndaqel (tafamidis). The only other treatment option was liver transplantation.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with ATTR amyloidosis because it works in a different way to existing treatment and early studies show that it might lead to significant reductions in amyloid levels. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
This medicine is a very short piece of synthetic RNA (a type of genetic material) which has been designed to attach to the part of the genetic material of cells that is responsible for producing the transthyretin protein, and prevent it from working. This reduces transthyretin production, thereby reducing the formation of amyloid deposits and relieving the symptoms of ATTR amyloidosis. The synthetic RNA is attached to another substance (a ligand) that allows the medicine to be taken up by the cells in the liver that are mainly responsible for producing transthyretin.
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 healthy volunteers 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 12 March 2014 recommending the granting of this designation.
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.
Alnylam UK Limited
5 New Street Square
London EC4A 3TW
United Kingdom
Tel. +44 (0)1255 444 400
E-mail: info@alnylam.com
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: