EU/3/14/1293

On 29 July 2014, orphan designation (EU/3/14/1293) was granted by the European Commission to GlaxoSmithKline Trading Services Limited, Ireland, for recombinant monoclonal antibody to human serum amyloid P component for the treatment of AL amyloidosis.

What is AL amyloidosis?

AL amyloidosis belongs to a group of diseases called systemic amyloidosis in which deposits of proteins (called amyloids) accumulate and cause damage in tissues and organs such as the kidneys, liver, gut, heart and nerves.

In AL amyloidosis, the deposits come from proteins (called immunoglobulin light chains) produced in excess by malfunctioning white blood cells in the bone marrow. These deposits also contain serum amyloid P (SAP), a protein normally found in blood.

Symptoms of the condition vary widely depending on which organs are affected by the deposits and how much deposits have accumulated in them.

AL amyloidosis is a life-threatening and long-term debilitating condition because of damage to organs, particularly the heart and kidneys.

What is the estimated number of patients affected by the condition?

At the time of designation, AL amyloidosis affected approximately 1.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 56,000 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).

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*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).

What treatments are available?

At the time of designation, no medicines were authorised in the EU for the treatment of AL amyloidosis. Patients often received treatment with medicines (chemotherapy) originally designed to treat cancers of white blood cells, in order to target the malfunctioning white blood cells. Stem-cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow) was used in a small group of newly diagnosed patients.

How is this medicine expected to work?

This medicine is an antibody, a type of protein designed to attach to the SAP protein in amyloid deposits. Patients are first treated with another medicine called carboxy pyrrolidine hexanoyl pyrrolidine carboxylate, which removes the SAP that normally circulates in the blood, to which the antibody would also attach. The antibody is expected to attach to the SAP in the amyloid deposits, thus stimulating the immune system to remove the unwanted material. This is expected to help reduce the deposits of amyloid that cause damage to the organs.

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 in patients with AL amyloidosis were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for AL amyloidosis 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 June 2014 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.

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