EU/3/05/271: Orphan designation for the treatment of visceral leishmaniasis

Leishmania are parasites that consist of one single cell, which are transmitted to humans through the bite of sand flies, mostly in the southern part of Europe and other parts of the world. Following the bite of the sandfly, the parasite is put in the skin where it will be taken up by specific cells of the body's defence system. The parasite will then multiply in that type of cell and spread through the body causing infections. Visceral leishmaniasis, the most severe form of leishmaniasis, will create infections in the cavities of the body where the major organs are located (most often in the abdomen). Patients having already an ongoing disease that suppress their own defense system (such as HIV infected patients) will be more sensitive to get infected by the Leishmania.

Visceral leishmaniasis is a chronically debilitating and life-threatening condition.

At the time of designation, visceral leishmaniasis affected approximately 0.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 4,600 people, and is below the threshold 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

Several products had been authorised for the condition in the Community at the time of submission of the application for orphan designation. Although a significant percentage of patients respond to the initial therapy, many of the immuno-suppressed patients tend to get the leishmania infection back and will not respond well to therapy anymore with the available products.

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 visceral leishmaniasis, particularly because it might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Paromomycin sulfate is an antibiotic (drugs that fight bacterial infections) belonging to a certain class, the so-called aminoglycosides, which also has shown activity against parasitic infections.

At the time of submission of the application for orphan designation, clinical trials in patients with visceral leishmaniasis were ongoing.

The medicinal product was not marketed anywhere worldwide for visceral leishmaniais or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 March 2005 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 European Union) 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.