EU/3/04/259: Orphan designation for the treatment of idiopathic pulmonary fibrosis

Fibrosis is the formation of scar tissue as part of the natural repair process of the body following tissue damage. Idiopathic pulmonary fibrosis consists of a chronic inflammation (a response of the body to the injury caused to the tissue) and progressive formation of fibrous tissue in the walls of the small chambers containing air in the lungs (alveoli). Since the injury causing these changes is unknown, it is called idiopathic. The progressive formation of scars impairs the normal functions of lung tissue, which are to enable exchange of oxygen and carbon dioxide between air and blood. The symptoms developed are persistent cough, progressive severe shortness of breath and recurrent lung infections.
Idiopathic pulmonary fibrosis is a chronically debilitating and life threatening disease due to the progression of symptoms, severe respiratory complications and short life expectancy.

At the time of designation, idiopathic pulmonary fibrosis affected between 0.6 and 2.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of between 28,000 and 110,000 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 based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004).

No satisfactory methods exist that were authorised at the time of application. Only symptomatic treatments to reduce the inflammation were used (corticosteroids and medicinal products that suppress the immune system) or for some patients lung transplantation was performed.

Scar formation (fibrosis) is regulated by several substances produced in the body during the inflammation that precedes fibrosis. Although the exact mechanism of scar formation (fibrosis) in idiopathic pulmonary fibrosis is not well understood, some substances such as free radicals (a chemically active molecular fragment which can damage the large molecules within cells) might play a role in the scar formation. Another substance, the so-called reduced glutathione, act against those free radicals. Acetylcysteine might stimulate the synthesis of reduced glutathione and thereby might help to prevent the formation of the fibrosis.

The effects of acetylcysteine were evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in patients with idiopathic pulmonary fibrosis were completed.
Acetylcysteine was not marketed anywhere worldwide for the treatment of idiopathic pulmonary fibrosis or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 8 December 2004 a positive opinion recommending the grant of the above-mentioned 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 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.