EU/3/14/1250: Orphan designation for the treatment of ATTR amyloidosis

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 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 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.