EU/3/18/2069: Orphan designation for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a long-term disease of the lungs characterised by the progressive deposition of collagen and fibrous tissue in the lungs. This causes the lung tissue to become thick and to form scars. As a result, the lungs no longer work normally, reducing the amount of oxygen that gets into the blood. Patients with idiopathic pulmonary fibrosis have a persistent cough, frequent lung infections and shortness of breath that worsens over time.

Idiopathic pulmonary fibrosis is a long-term debilitating and life-threatening disease because the lungs gradually lose their ability to work properly.

At the time of designation, idiopathic pulmonary fibrosis affected approximately 3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 155,000 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).

At the time of designation, Esbriet (pirfenidone) and Ofev (nintedanib) were authorised in the EU to treat idiopathic pulmonary fibrosis.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with idiopathic pulmonary fibrosis because laboratory studies suggested that it was as effective as the authorised treatments and could reduce development of fibrous tissue when given by inhalation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The exact way that tilorone works in this condition is not fully understood, but it is thought to act in several complementary ways. These include blocking the action of a substance called gremlin-1, which is present at high levels in the lungs of patients with idiopathic pulmonary fibrosis. Gremlin-1 stimulates the development of fibrous tissue by interfering with protective molecules called bone morphogenetic proteins (BMP). In addition, tilorone is thought to reduce the activity of another substance, TGF-beta, that is implicated in the development of fibrous tissue. Together these actions are expected to slow down the progression of idiopathic pulmonary fibrosis.

The effects of tilorone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with tilorone in patients with idiopathic pulmonary fibrosis had been started.

At the time of submission, the medicine was authorised in Russia and some other non-EU countries for viral infections.

At the time of submission, tilorone was not authorised anywhere in the EU for idiopathic pulmonary fibrosis or designated as an 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 19 July 2018 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.