Overview

On 26 March 2014, orphan designation (EU/3/14/1250) was granted by the European Commission to Isis USA Ltd, United Kingdom, for phosphorothioate oligonucleotide targeted to transthyretin for the treatment of ATTR amyloidosis.

In April 2016, Isis USA Ltd changed name to Ionis USA Ltd.

Phosphorothioate oligonucleotide targeted to transthyretin has been authorised in the EU as Tegsedi since 6 July 2018.

This medicine is now known as inotersen.

The sponsorship was transferred to Akcea Therapeutics UK Ltd., United Kingdom, in October 2018.

The sponsorship was transferred to Akcea Therapeutics Ireland Limited, Ireland, in February 2019.

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 consist 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 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 the amyloid deposits may accumulate in the heart and cause fatal heart conditions.

At the time of designation, ATTR amyloidosis affected less than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 153,000 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. This represents a population of 511,100,000 (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 the medicine 'phosphorothioate oligonucleotide targeted to transthyretin' might be of significant benefit for patients with ATTR amyloidosis because it works in a different way to existing treatment and early studies in experimental models show that it might improve the outcome of patients at different stages of the disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is an 'antisense oligonucleotide', a very short piece of synthetic genetic material which has been designed to attach to the genetic material of cell responsible for producing the transthyretin protein. This is expected to reduce transthyretin production, thereby reducing the formation of amyloids and relieving the symptoms of ATTR amyloidosis.

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. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 2014 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.

EU/3/14/1250: Public summary of opinion on orphan designation: Phosphorothioate oligonucleotide targeted to transthyretin for the treatment of ATTR amyloidosis

Key facts

Active substance
Phosphorothioate oligonucleotide targeted to transthyretin (inotersen)
Medicine name
Tegsedi
Intended use
Treatment of ATTR amyloidosis
Orphan designation status
Positive
EU designation number
EU/3/14/1250
Date of designation
Sponsor

Akcea Therapeutics Ireland Limited
St. James House
72 Adelaide Road
Dublin 2
Co. Dublin
D02 Y017
Ireland
E-mail: info@akceatx.com

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Tegsedi at the time of marketing authorisation, and confirmed that the orphan designation should be maintained.

More information is available in the Tegsedi : Orphan maintenance assessment report (initial authorisation).

Update history

DateUpdate
January 2023The sponsor's address was updated.

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:

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:

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