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Orphan designation

On 15 April 2011, orphan designation (EU/3/11/857) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for synthetic double-stranded siRNA oligonucleotide directed against transthyretin mRNA for the treatment of familial amyloid polyneuropathy.

The sponsorship was transferred to Alnylam UK Limited, United Kingdom, in November 2014.

What is familial amyloid polyneuropathy?

Familial amyloid polyneuropathy (FAP) is a hereditary (‘familial’) disease caused by a defective gene for transthyretin, a protein that transports various substances in the blood. Transthyretin is primarily produced in the liver.

Patients with FAP have an abnormal transthyretin protein that breaks up easily and accumulates in various tissues in the body, especially tissues of the nervous system, in the form of insoluble, waxy ‘amyloid’ structures. The condition mainly affects the nervous system causing 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.

FAP is a long-term debilitating disease due to the progressive worsening of nervous system symptoms. It is also life threatening because the amyloid deposits may accumulate in the heart and cause fatal heart conditions.

What is the estimated number of patients?

At the time of designation, FAP affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

What treatments are available?

At the time of designation, no satisfactory methods had been authorised in the EU for the treatment of FAP. The only available treatment was liver transplantation.

How is this medicine expected to work?

The medicine is made of a small strand of synthetic genetic material, called ‘small interfering RNA’ (siRNA), that interferes with the expression of certain genes. It has been designed to target the defective gene in patients with FAP, where it is expected to block the production of the abnormal transthyretin protein in the liver, thereby reducing the accumulation of amyloid deposits in the tissues and slowing down the progression of the disease.

What is the stage of development of this medicine?

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 including patients with FAP were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for FAP 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 January 2011 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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

Product details for <p>Synthetic double-stranded siRNA oligonucleotide directed against transthyretin mRNA</p>
Active substanceSynthetic double-stranded siRNA oligonucleotide directed against transthyretin mRNA
Medicine Name
Disease/conditionTreatment of familial amyloid polyneuropathy
Date of decision15/04/2011
Orphan decision numberEU/3/11/857

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details

Alnylam UK Limited
5 New Street Square
London EC4A 3TW
United Kingdom
Tel. +44 (0)1895 876573

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.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.