EU/3/02/093: Orphan designation for the treatment of intestinal graft-versus-host disease

Bone marrow transplantation is primarily utilised in the treatment of patients with malignant tumours or with blood diseases, such as leukemias and marrow dysplasias. A frequent complication of transplantation is the development of GvHD. This disease process involves a reaction between the donor cells and the recipient's native tissues. GvHD occurs in acute and chronic form. The anatomical sites most likely affected in acute GvHD are the gastrointestinal tract, the skin, and the liver. Chronic GvHD involves a much wider range of tissues than the acute form. Any portion of the gastro-intestinal tract may be involved. The condition is chronically debilitating and life-threatening.

At the time of designation, intestinal graft versus host disease affected between 0.1 and 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of between 3,800 and 7,500 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: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 377,000,000 (Eurostat 2001) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

The methods of treatment were authorised for GvHD in the Community, at the time of submission of the application for orphan designation, consisted of systemic corticosteroids administered at high doses. Other therapies include various immunosuppressants. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product might be of potential significant benefit for the treatment of intestinal GvHD, particularly in terms of limiting toxicity.

Corticosteroids exert their anti-inflammatory effects by causing a decrease in the numbers of circulating white blood cells. Several immune factors are inhibited. Beclomethasone 17,21-dipropionate is a corticosteroid with potent local anti-inflammatory effect.

At the time of submission of the application for orphan designation, clinical trials in patients with GvHD with gastrointestinal symptoms were ongoing

Beclomethasone 17,21-dipropionate (oral use) had not been marketed anywhere worldwide for intestinal GvHD, at the time of submission. Orphan designation of oral beclomethasone 17,21-dipropionate had been granted by the United States Food and Drug Administration (FDA) for oral administration in the treatment of intestinal GvHD.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 January 2002 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.