EU/3/13/1123

On 26 April 2013 orphan designation (EU/3/13/1123) was granted by the European Commission to Boehringer Ingelheim International GmbH, Germany, for nintedanib for the treatment of idiopathic pulmonary fibrosis.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is 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 become unable to work normally, reducing the transfer of oxygen from the air 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 life-threatening and long-term debilitating disease because the lungs gradually lose their ability to work properly.

What is the estimated number of patients affected by the condition?

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 154,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 28), Norway, Iceland and Liechtenstein.
At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, Esbriet (pirfenidone) was the only medicine authorised in the EU to treat mild to moderate idiopathic pulmonary fibrosis.

The sponsor has provided sufficient information to show that nintedanib might be of significant benefit for patients with idiopathic pulmonary fibrosis based on results of early studies which showed fewer declines in lung function with nintedanib treatment compared with placebo (a dummy treatment). In addition, nintedanib showed reductions in exacerbations (flare-ups of symptoms) and an improvement in patients’ quality of life.

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?

Enzymes called tyrosine kinases are known to be involved in development of idiopathic pulmonary fibrosis via a number of chemical pathways in the lungs that are related to the generation of fibrous tissue.

Nintedanib is a ‘tyrosine-kinase inhibitor’, which means that it blocks the actions of these enzymes, thereby interrupting the disease pathways and helping to reduce the formation of fibrous tissue in the lungs.

What is the stage of development of this medicine?

The effects of nintedanib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with nintedanib in patients with idiopathic pulmonary fibrosis were ongoing.

At the time of submission, nintedanib was not authorised anywhere in the EU for idiopathic pulmonary fibrosis. Orphan designation of nintedanib has been granted in the United States and in Japan for idiopathic pulmonary fibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 March 2013 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;
• 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.

During its meeting of 9 to 11 December 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/13/1123 for Ofev (nintedanib)as an orphan medicinal product for the treatment of idiopathic pulmonary fibrosis. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with idiopathic pulmonary fibrosis. The COMP recommended that the orphan designation of the medicine be maintained¹.

¹The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Ofev for the treatment of idiopathic pulmonary fibrosis in adults.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of idiopathic pulmonary fibrosis’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2013. Idiopathic pulmonary fibrosis remains a debilitating and life-threatening condition because the lungs gradually lose their ability to work properly.

Prevalence of the condition

The sponsor performed a search of the scientific literature and concluded that no publications are available which suggest a change in prevalence of idiopathic pulmonary fibrosis.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of idiopathic pulmonary fibrosis remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be not more than 3 people in 10,000. This is equivalent to a total of not more than 153,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, Esbriet (pirfenidone) was the only medicine authorised in the EU to treat mild to moderate idiopathic pulmonary fibrosis.

Significant benefit of Ofev

The COMP concluded that the claim of a significant benefit of Ofev in idiopathic pulmonary fibrosis is justified because Ofev can also be used to treat those patients with disease severity other than mild to moderate, for whom no treatment is authorised.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Ofev is of significant benefit to patients affected by idiopathic pulmonary fibrosis.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Ofev still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.