EU/3/09/704

On 28 January 2010, orphan designation (EU/3/09/704) was granted by the European Commission to Italfarmaco S.p.A., Italy, for givinostat for the treatment of systemic-onset juvenile idiopathic arthritis.

What is systemic-onset juvenile idiopathic arthritis?

Arthritis is inflammation of the joints, which results in pain and limited functioning of the affected joints. There are many forms of arthritis that differ in terms of number and type of the joints affected and the age of onset. Systemic-onset juvenile idiopathic arthritis is a type of arthritis that starts before the age of 16 years and is associated with other symptoms, such as daily bouts of high fever and rash, and stomach ache. ‘Idiopathic’ means that the cause of the disease is unknown.

Systemic-onset juvenile arthritis is a long-term debilitating disease because of its recurrent episodes of arthritis and fever, which have an impact on the child’s growth and development. The disease may also be life threatening due to life-threatening complications, such as infection or ‘macrophage activation syndrome’, a condition where some cells of the immune system become overactive and attack organs such as the spleen.

What is the estimated number of patients?

At the time of designation, systemic-onset juvenile idiopathic arthritis affected less than 0.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 25,000 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 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. This represents a population of 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of designation, several medicines with anti-inflammatory activity were authorised in the EU for idiopathic juvenile arthritis. In addition, there were other treatments not specifically authorised but used for systemic-onset juvenile idiopathic arthritis, including thalidomide, immunosuppressive medicines (medicines that reduce the activity of the immune system) and autologous bone marrow transplantation. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow previously obtained from the same patient.

The sponsor has provided sufficient information to show that givinostat might be of significant benefit for patients with systemic-onset juvenile idiopathic arthritis because it works in a different way to existing treatments, and because early studies in experimental models indicate that it might improve the treatment of patients with this condition. These assumptions 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?

Givinostat is expected to work in systemic-onset juvenile idiopathic arthritis by blocking the production of several chemical messengers called ‘pro-inflammatory cytokines’. These include interleukin-1 (IL-1), IL-6 and tumour necrosis factor-alpha (TNF-alpha). These messengers are produced in high levels in patients with systemic-onset juvenile idiopathic arthritis, causing inflammation of the joints and joint damage. By blocking their production, givinostat is expected to relieve the symptoms of the disease.

What is the stage of development of this medicine?

The effects of givinostat have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with systemic-onset juvenile idiopathic arthritis were ongoing.

At the time of submission, givinostat was not authorised anywhere in the EU for systemic-onset juvenile idiopathic arthritis or designated as 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 5 November 2009 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;
• ither the rarity of the condition (affecting not more than 5 in 10,000 people in the Community) 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.