EU/3/16/1780

On 18 November 2016, orphan designation (EU/3/16/1780) was granted by the European Commission to Janssen-Cilag International N.V, Belgium, for ibrutinib for the treatment of graft-versus-host disease.

What is graft-versus-host disease?

Graft-versus-host disease is a complication that can affect patients who have had allogeneic haematopoietic (blood) stem-cell transplantation to treat diseases of the blood such as leukaemia (a cancer of the white blood cells). The procedure involves a patient receiving stem cells from a donor to help restore the bone marrow, which produces new healthy blood cells.

Graft-versus-host disease occurs when transplanted cells recognise the patient’s body as ‘foreign’ and attack the patient’s organs, such as the stomach, gut, skin and liver, leading to organ damage. The disease may happen shortly after transplantation or later on, in which case a wider range of organs can be involved.

Graft-versus-host disease is a serious and life-threatening disease with a high mortality rate.

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

At the time of designation, graft-versus-host disease affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 21,000 people¹, 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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¹Disclaimer: 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, several medicines were authorised in the European Union (EU) for the treatment of graft-versus-host disease, such as ciclosporin and corticosteroids. Treatment aimed to reduce the activity of transplanted cells involved in graft-versus-host disease, thereby reducing their ability to attack the patient’s organs.

The sponsor has provided sufficient information to show that ibrutinib might be of significant benefit for patients with graft-versus-host disease because early studies found improvement in patients who had not improved on medicines authorised for the condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Ibrutinib blocks two enzymes. The first is called Bruton’s tyrosine kinase (Btk), which is mostly found in B cells, and the second is interleukin-2-inducible T-cell kinase (ITK), which stimulates T cells. B cells and T cells are part of the immune system, the body’s natural defences. Both B cells and T cells in the transplant are thought to be involved in the attack on the patient's organs. By blocking Btk and ITK, ibrutinib is expected to reduce the activity of both types of cells and improve the symptoms of graft-versus-host disease.

What is the stage of development of this medicine?

The effects of ibrutinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with ibrutinib in patients with graft-versus-host disease were ongoing.

At the time of submission, ibrutinib was authorised in the EU under the name Imbruvica for mantle cell lymphoma, chronic lymphocytic leukaemia and Waldenström’s macroglobulinaemia.

At the time of submission, the medicine was not authorised anywhere in the EU for graft-versus-host disease. Orphan designation of ibrutinib had been granted in the United States for graft-versus-host disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 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.