EU/3/05/318: Orphan designation for the prevention of tuberculosis disease in Bacille-Calmette-Guerin-vaccinated individuals

Tuberculosis (TB) is an infection caused by a group of bacteria called Mycobacteria. It spreads from person to person by inhaling the infected airborne droplets generated by sneezing and coughing. The manifestation of the disease is variable and not all patients who are infected will develop the disease. The disease is characterised by fever, cough and breathing difficulties. Granulomas (accumulations of large numbersof cells leading to chronic inflammatory lesions) can develop in any body tissue by the formation of tubercles. TB most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, genitourinary system, bones and joints. Tuberculosis is a life-threatening condition.

The BCG vaccine was authorised for prevention of tuberculosis in the Community at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that recombinant modified vaccinia virus Ankara expressing tuberculosis antigen 85A might be of potential significant benefit for the prevention of tuberculosis as it is designed to enhance (boost) the effect of the BCG vaccine. This assumption of benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Usually applications for orphan designation are made on the grounds of the rarity of the disease. However, an alternative criterion based on the expected return on investment also exists.

According to the information provided by the sponsor, considering the estimated total discovery and development costs of bringing recombinant modified vaccinia virus Ankara expressing tuberculosis antigen 85A to the market, and the expected revenue that will be generated from the sales of the vaccine in the Community, it is unlikely that sufficient return will be generated to justify the necessary investment.

BCG is a vaccine used for tuberculosis prevention. Administering BCG exposes the body's defence system (immune system) to a microorganism similar to the Mycobacterium, aimed at building an immune response against the infection. Recombinant modified vaccinia virus Ankara expressing tuberculosis antigen 85A is a vaccine that has been developed to boost the body immune response following BCG vaccination. The vaccine is expected to boost the individual's immune system against the Mycobacterium and thereby might improve the body's protection against the development of the disease.

The evaluation of the effects of recombinant modified vaccinia virus Ankara expressing tuberculosis antigen 85A in experimental models is ongoing.

At the time of submission of the application for orphan designation, clinical trials in BCG vaccinated individuals were ongoing.

Recombinant modified vaccinia virus Ankara expressing tuberculosis antigen 85A was not authorised anywhere worldwide for prevention of tuberculosis disease in BCG-vaccinated individuals or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2005 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.