EU/3/19/2200 : Orphan designation for the treatment of nontuberculous mycobacterial lung disease

Nontuberculous mycobacterial lung disease is an infection of the lungs by nontuberculous mycobacteria.

Nontuberculous mycobacteria (also known as environmental mycobacteria) are bacteria found widely in the environment, such as in water and in soil, but unlike other species of mycobacteria that cause tuberculosis and leprosy, they do not usually cause disease in people. When they do cause disease, patients are infected by coming into direct contact with the bacteria in the environment and not from close contact with people who have the infection.

Lung infection with nontuberculous mycobacteria typically occurs in patients who already have lung disease or who have a weakened immune system. Symptoms include long-term coughing, excess sputum (phlegm) and tiredness and, less commonly, coughing up blood, difficulty breathing, fever and weight loss.

Nontuberculous mycobacterial lung disease is debilitating in the long term because of lung damage.

At the time of designation, nontuberculous mycobacterial lung disease affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 people¹, 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).

¹Disclaimer: 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. This represents a population of 518,400,000 (Eurostat 2019).

At the time of designation, a number of antibiotics were authorised in the EU for treating nontuberculous mycobacterial lung disease.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with nontuberculous mycobacterial lung disease. Studies have shown that adding this medicine to standard treatments could clear the bacteria faster than using only standard treatments. Furthermore, laboratory studies indicate that this medicine, when inhaled, could be more effective than oral medicines containing the same active substance.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Clofazimine is an antibiotic that acts against mycobacteria. It does so by interfering with the process through which the bacteria produce energy and by causing the release of toxic substances that stop the bacteria from growing.

Clofazimine has been authorised for use by mouth in the treatment of leprosy (a mycobacterial infection) in some EU countries. As this medicine is to be inhaled, it will be delivered directly to the lungs where its effects are needed.

The effects of clofazimine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with nontuberculous mycobacterial lung disease had been started.

At the time of submission, use of this medicine by inhalation was not authorised anywhere in the EU for the treatment of nontuberculous mycobacterial lung disease. Orphan designation had been granted in the United States for the treatment of ‘pulmonary nontuberculous mycobacterial infections’.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 July 2019, 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.