EU/3/17/1901: Orphan designation for the treatment of naevoid basal-cell carcinoma syndrome (Gorlin syndrome)

Naevoid basal-cell carcinoma syndrome (also known as Gorlin syndrome) is a genetic condition where patients have a high risk of developing cancerous and non-cancerous (benign) tumours.

In people with Gorlin syndrome, the most common cancer is basal-cell carcinoma, a slow-growing type of skin cancer, which usually develops on the face, chest and back. Most people also develop non-cancerous tumours of the jaw which cause face swelling and problems with teeth. Skeletal problems in the spine, ribs and skull are also common.

Gorlin syndrome is a long-term debilitating condition because of the multiple tumours which can lead to deformities.

At the time of designation, Gorlin syndrome affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).

At the time of designation, imiquimod, sonidegib and vismodegib were authorised in the EU for treating basal-cell carcinoma.

The sponsor has provided sufficient information to show that itraconazole might be of significant benefit for patients with Gorlin syndrome. Early results from an ongoing study showed that it reduced tumour size in patients for whom current treatments did not work. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Itraconazole has been used to treat fungal infections for several years. In Gorlin syndrome, it is expected to work by blocking 'the Hedgehog signalling pathway'. In Gorlin syndrome, the Hedgehog signalling pathway becomes abnormally active and leads to the growth and spread of the cancerous cells. Itraconazole is thought to attach to a protein called 'SMO', which is involved in activating the Hedgehog signalling pathway. By attaching to SMO, itraconazole is expected to block this pathway, thereby slowing down the growth and spread of the cancer cells in Gorlin syndrome.

The effects of itraconazole have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with itraconazole in patients with Gorlin syndrome were ongoing.

At the time of submission, itraconazole was not authorised anywhere in the EU for Gorlin syndrome. Orphan designation of itraconazole had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2017 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.