EU/3/10/786: Orphan designation for the treatment of tuberculosis

Tuberculosis (TB) is an infection caused by bacteria called Mycobacterium tuberculosis. People become infected by inhaling infected droplets from the coughs or sneezes 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 a 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 is equivalent to a total of around 101,000 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 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. This represents a population of 506,500,000 (Eurostat 2010).

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

The sponsor has provided sufficient information to show that heat-killed Mycobacterium vaccae (whole cell) might be of significant benefit for patients with tuberculosis because it works in a different way to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Heat-killed Mycobacterium vaccae (whole cell) is expected to act as an 'immunotherapeutic medicine'. This means that it is expected to modify the way the immune system responds to TB to help the body fight the disease more effectively.

The medicine contains Mycobacterium vaccae, a bacterium from the same family as the bacteria that cause TB, which has been killed with heat. It is expected to increase the ability of the immune system to fight the TB bacteria. In addition, it may reduce some of the undesirable immune responses to the TB bacteria that can cause harm to the patient, such as damage to the lung tissue and weight loss. The medicine is intended to be used as an 'add on' to other medicines.

The effects of heat-killed Mycobacterium vaccae (whole cell) have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a series of clinical trials had been completed with a previous formulation of the product but no clinical trials with the proposed formulation of heat-killed Mycobacterium vaccae (whole cell) in patients with tuberculosis had been started.

At the time of submission, heat-killed Mycobacterium vaccae (whole cell) was not authorised anywhere in the EU for tuberculosis 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 2 June 2010 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 European Union) 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.