EU/3/12/1060: Orphan designation for the treatment of systemic light chain amyloidosis

Amyloidosis is a group of diseases in which deposits of proteins (called amyloids) accumulate in organs of the body, such as the heart and kidneys, damaging them and preventing them from working properly. In systemic light chain amyloidosis, the deposits are made of a blood protein called 'immunoglobulin light chain' produced by abnormal blood cells. This condition often occurs in patients with other blood disorders, such as multiple myeloma.

Systemic light chain amyloidosis is a long-term debilitating and life-threatening condition mainly due to damage to the heart.

At the time of designation, systemic light chain amyloidosis affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 36,000 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. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

At the time of designation, there were no treatments authorised in the EU for systemic light chain amyloidosis. Patients were treated with anticancer medicines to kill the abnormal blood cells responsible for the production of immunoglobulin light chain. Some patients also underwent stem cell transplantation. This is a complex procedure where the patient receives stem cells to help restore the bone marrow (the spongy tissue inside the large bones where blood cells are produced).

Ixazomib is expected to work by blocking the proteasome, which is a system within the cells that breaks down proteins when they are no longer needed. By blocking the proteasome of the abnormal blood cells in systemic light chain amyloidosis, the proteins in these cells are not broken down. As a result, the cells eventually die. This is expected to help improve the symptoms of the disease.

Ixazomib is expected to work by blocking the proteasome, which is a system within the cells that breaks down proteins when they are no longer needed. By blocking the proteasome of the abnormal blood cells in systemic light chain amyloidosis, the proteins in these cells are not broken down. As a result, the cells eventually die. This is expected to help improve the symptoms of the disease.

The effects of ixazomib have been evaluated in experimental models.

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

At the time of submission, ixazomib was not authorised anywhere in the EU for systemic light chain amyloidosis. Orphan designation of ixazomib had been granted in the United States of America for this condition.

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.