EU/3/17/1857

On 20 March 2017, orphan designation (EU/3/17/1857) was granted by the European Commission to Grupo Español de Tumores Huérfanos e Infrecuentes (GETHI), Spain, for ketoconazole for the treatment of granulosa cell tumours.

What are granulosa cell tumours?

Granulosa cell tumours are a cancer of the ovaries (female reproductive organs that produce eggs). This type of cancer can also occur in testicles in males. In females, it often increases the production of the hormone oestrogen. Symptoms include stomach pain, increase in stomach size, problems with passing urine, constipation, dizziness, menstrual problems in women and early puberty in girls.

Granulosa cell tumours can occur in adults and children. They are debilitating and life threatening because the cancer can worsen and spread to other parts of the body.

What is the estimated number of patients affected by the condition?

At the time of designation, granulosa cell tumours affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017)

What treatments are available?

At the time of designation, several medicines were authorised in the EU for the treatment of granulosa cell tumours. Treatments included surgery and chemotherapy (medicines to treat cancer). The choice of treatment depended mainly on how advanced the disease was.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with granulosa cell tumours because early studies showed that combining this medicine with the standard treatment stopped progression of the cancer for a long time in patients whose disease had come back after all available treatment options. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Ketoconazole blocks the activity of enzymes involved in the production of oestrogen and other hormones in patients with granulosa cell tumours. By blocking the action of these enzymes, ketoconazole is expected to reduce the symptoms caused by increased hormone levels in the disease. The medicine is available as tablets.

What is the stage of development of this medicine?

The effects of ketoconazole have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with ketoconazole in patients with granulosa cell tumours had been carried out.

At the time of submission, ketoconazole taken by mouth was authorised in the EU for Cushing’s syndrome. It was not authorised anywhere in the EU for granulosa cell tumours 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 16 February 2017 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.