EU/3/10/826

Tuberculosis (TB) is an infectious disease caused by bacteria called Mycobacterium tuberculosis. People become infected by inhaling infected droplets from the cough or sneeze of people who have the disease. TB primarily affects the lungs (when it is called pulmonary TB) but it can also spread to other parts of the body, such as the bones or the nervous system. The symptoms of TB include persistent cough, fever, weight loss and night sweats. Not everyone infected will develop the symptoms of the disease.

TB is a long-term debilitating disease. When left untreated, the disease may be life-threatening, mainly because of the severe damage to the lungs that does not allow the patient to breathe normally, and because the bacteria causing the disease are often resistant to existing treatments.

At the time of designation, TB affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 101,000 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).

*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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, several antibiotics were authorised in the EU to treat TB. These were used in combination and for long periods of time, normally at least six months.

The sponsor has provided sufficient information to show that para-aminosalicylic acid might be of significant benefit for patients with TB because it is expected to improve the treatment of patients with TB that is resistant to many other medicines, and because it will be available as a gastroresistant granule formulation that is expected to cause fewer side effects. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Medicines containing para-aminosalicylic acid have been used in combination with other medicines to treat TB since the 1940s. Para-aminosalicylic acid is a 'bacteriostatic'. This means that it prevents the bacteria from growing and multiplying without actually killing them. It does this by blocking the synthesis (manufacture) of folic acid, which the bacteria need to grow and multiply, and of mycobactin, a component of their cell wall. These actions have the effect of stopping the growth of bacteria also in patient with TB that is resistant to other antibiotics like streptomycin and isoniazid.

In this medicine, para-aminosalicylic acid is expected to be available as gastroresistant granules that allow the para-aminosalicylic acid to reach the intestine without being released in the stomach, thus avoiding irritation in the stomach and causing fewer side effects.

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with para-aminosalicylic acid in patients with TB had finished.

At the time of submission, para-aminosalicylic acid was authorised in the United States and Russia for TB.

At the time of submission, the medicine was not authorised anywhere in the EU for TB. Orphan designation of para-aminosalicylic acid for TB had been granted in the United States.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2010 recommending the granting of this designation.

Update: para-aminosalicylic acid (Granupas, previously Para-aminosalicylic acid Lucane) has been authorised in the EU since 7 April 2014 for use as part of an appropriate combination regimen for multi-drug resistant tuberculosis in adults and paediatric patients from 28 days of age and older when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

• 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.