EU/3/12/1066: Orphan designation for the treatment of senile systemic amyloidosis

Senile systemic amyloidosis is an age-related type of amyloid disease, in which deposits of proteins (called amyloids) accumulate in the heart and, more rarely, in other organs.

The disease mainly affects the elderly, particularly elderly men, and is linked to ageing. As people age, a protein called transthyretin, which is involved in the transport of substances in the blood, starts to break up and lose its function. The broken up parts of the protein then form deposits that accumulate as amyloids in the heart, where they can cause damage to the heart muscle.

Senile systemic amyloidosis is a life-threatening disease because of the severe damage to the heart that leads to heart failure.

At the time of designation, senile systemic amyloidosis affected approximately 3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 152,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, no satisfactory methods were authorised in the EU for treating senile systemic amyloidosis. Treatments focused at improving the functioning of the heart, and included diuretics and pacemakers.

Tafamidis is expected to attach to and stabilise the transthyretin protein. The normal form of the protein is as a homotetramer, which means that it is formed of four identical protein chains linked to each other.

By attaching to transthyretin, the medicine is expected to keep the protein in its homotetramer form, preventing it from breaking up and thereby decreasing the amount of harmful amyloid deposits in the heart.

The effects of tafamidis have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with tafamidis in patients with senile systemic amyloidosis were ongoing.

At the time of submission, tafamidis was authorised in the EU for the treatment of transthyretin amyloidosis.

At the time of submission, tafamidis was not authorised anywhere in the EU for senile systemic amyloidosis. Orphan designation of tafamidis had been granted in the United States of America for symptomatic transthyretin amyloid cardiomyopathy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 October 2012 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.