EU/3/05/321: Orphan designation for the treatment of primary malignant bone tumours

Tumours that begin in the bone tissues are known as primary malignant bone tumours. Primary malignant bone tumours are classified by the type of tissue they originate, the most common being bone sarcomas. They can occur in any bone of the body and they spread almost exclusively through the blood. There are many types of primary malignant bone tumours, which tend to behave differently. Primary malignant bone tumours are a serious condition, potentially debilitating and life-threatening.

At the time of designation, primary malignant bone tumours affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 47,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

Surgery is currently the main choice of therapy for primary malignant bone tumours usually combined with chemotherapy (using drugs to kill cancer cells) prior to or after surgery. Several products were authorised for the condition in some countries in the Community at the time of submission of the application for orphan drug designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that AP23573 might be of potential significant benefit for the treatment of primary malignant bone tumours mainly because it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Rapamycin is a kind of antibiotic (chemical substances which have the capacity to block the growth of or kill microorganisms, such as bacteria). AP23573 is similar to rapamycin (a so-called rapamycin analogue), but with a slightly different structure. Specific receptors (cell proteins that can only bind other substances having a specific shape, in order to activate, or block, certain biologic reactions of the cell), the so-called mammalian target of rapamycin (mTOR), can bind to the rapamycin and its analogues. mTOR plays a role in a cascade of molecular reactions to bring a certain signal from outside the cell into the cell thereby controlling the growth of the cells. Rapamycin and its analogues can block (inhibit) the mTOR. AP23573 might, by inhibition of this receptor, help in slowing down or stopping the further growth of the cancer cells.

The effects of AP23573 were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with primary malignant bone tumours were ongoing.

AP23573 was not authorised anywhere worldwide for primary malignant bone tumours 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 Community) 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.