EU/3/04/241: 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. 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 and progressive severe shortness of breath.

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 not more than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 139,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (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. These substances stimulate the so-called fibroblasts (the main cells responsible for formation of the fibrosis). Although it is not yet fully understood how pirfenidone acts in idiopathic pulmonary fibrosis, it could reduce the action on these substances and thereby reduce the scar formation.

The effects of pirfenidone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, several clinical trials in patients with idiopathic pulmonary fibrosis had been completed.

Pirfenidone was not marketed anywhere worldwide for idiopathic pulmonary fibrosis, at the time of submission. Orphan designation of pirfenidone was granted in the United States for idiopathic pulmonary fibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2004 recommending the granting of this designation.

Update: Pirfenidone (Esbriet) was authorised in the EU on 28 February 2011. Esbriet is indicated in adults for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF).

• 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.