EU/3/06/404: Orphan designation for the treatment of Li Fraumeni Syndrome

Patients affected by Li-Fraumeni syndrome have a hereditary disorder that increases their risk for several cancer types with early life onset. Cancer types that are common in patients with Li-Fraumeni syndrome include osteosarcoma (cancers of the skeleton and bones), breast cancer, brain cancer, adrenocortical cancer (cancer of the adrenal glands) and leukaemia (cancer of the white blood cells). The syndrome is caused by a defect in a gene that regulates the protein p53. This protein is very important for cells' natural ability to recognise when they have been damaged. When cells lack this ability or this ability is decreased, the risk of cells starting to divide and grow uncontrollably and develop tumours increases by many folds. Li-Fraumeni syndrome is chronically debilitating and life-threatening because of the high risk for affected patients to develop several cancer tumours at an early age.

At the time of designation Li-Fraumeni syndrome affected less than 0.05 in 10,000 people in the European Union (EU)*. This is equivalent to a total of less than 2,300 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 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 459,700,000 (Eurostat 2004).

Cancer tumours in Li-Fraumeni syndrome patients are treated in the same way as cancer tumours in other patients. Treatment depends on many factors including the type of cancer, age, sex and how advanced the tumour is at diagnosis. Most treatments for the type of cancers occurring in Li-Fraumeni patients are chemotherapy (using drugs to kill cancer cells).

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that adenoviral vector containing human p53 gene might be of potential significant benefit for the treatment of Li-Fraumeni syndrome, mainly because it has a new mechanism of action and may be used in combination with other treatments. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Adenoviral vector containing human p53 gene is a virus-like particle that is designed to deliver healthy copies of the defective p53 gene to the cancer cells. According to the sponsor, adenoviral vector containing human p53 gene will, by providing the tumour cells with p53, make them more susceptible to be destroyed by the damage that chemotherapy drugs cause.

The effects of adenoviral vector containing human p53 gene were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with Li-Fraumeni syndrome were ongoing.

Adenoviral vector containing human p53 gene was not authorised anywhere worldwide for the treatment of Li-Fraumeni syndrome, at the time of submission of the application for orphan drug designation. Orphan designation of adenoviral vector containing human p53 gene was granted in the United States for the treatment of head and neck cancer.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 September 2006 a positive opinion recommending the grant of the above-mentioned 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.