EU/3/12/1044: Orphan designation for the diagnosis of positive folate-receptor status in ovarian cancer

Ovarian cancer is cancer of the ovaries (two organs in the female reproductive system that produce eggs). Most ovarian cancers occur in women over the age of 50 years. Due to the absence of symptoms in the early stages of the disease, the majority of patients are diagnosed when the cancer has spread to other parts of the body.

Most ovarian cancers are 'folate-receptor positive'. This means that the surface of the cancer cell contains high amounts of a receptor, which folic acid (a vitamin required for cell division) attaches to. This receptor can be targeted for treatment.

Ovarian cancer is a life-threatening disease that is associated with poor long-term survival.

At the time of designation, the number of patients eligible for diagnosis of positive folate receptor status in ovarian cancer was estimated to be not more than 1.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more than 66,000 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. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, there were no satisfactory methods of diagnosing positive folate-receptor status in ovarian cancer in the EU. Existing methods were limited to detecting the presence of ovarian cancer cells. They included vaginal examination to check for any visible abnormalities of the womb or ovaries. In addition, blood tests and ultrasound were used to help identify masses in the abdomen. If a mass was discovered, the patient underwent surgery to determine the nature of the mass.

Folic-acid injections are used to improve the image on scans for diagnosing positive folate-receptor status in ovarian cancer. It is given before the injection of another medicine that is radioactive and also contains folic acid. The radioactive medicine can enter the cancer cells by attaching to their folate receptors and once inside it emits radiation which can be seen as an image on a scan.

The folic-acid injections are given before the radioactive medicine as this has been shown to improve the quality of the image on the scan. This is because the folic acid attaches to many receptors in non-cancer cells, thereby ensuring that more of the radioactive medicine attaches to the receptors on the cancer cells.

The effects of folic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with folic acid in patients with ovarian cancer were ongoing.

At the time of submission, folic acid was not authorised anywhere in the EU for the diagnosis of positive folate-receptor status in ovarian cancer or designated as an orphan medicinal product elsewhere for diagnosing this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 July 2012 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 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.