EU/3/18/2050: Orphan designation for the treatment of neurofibromatosis type 1

Neurofibromatosis type 1 is an inherited disease in which the patient develops benign (non-cancerous) tumours along the nerves. The severity of the disease varies from patient to patient, and symptoms include pale, coffee-coloured patches, freckles in unusual places (such as the armpits, groin and under the breasts), high blood pressure, problems with the bones, eyes and nervous system, learning difficulty and short stature. Patients can also develop cancer, including cancer of the optic nerve (the nerve that sends signals from the eye to the brain).

The disease is caused by mutations (changes) in a gene called NF1, which leads to uncontrolled growth of cells in the nervous system.

Neurofibromatosis type 1 is a debilitating disease because of the damage caused by the tumours. The disease may also be life threatening due to the increased risk of developing cancer.

At the time of designation, neurofibromatosis type 1 affected approximately 3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 155,000 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 517,400,000 (Eurostat 2018).

At the time of designation, there were no treatments authorised in the EU for neurofibromatosis type 1. Surgery was used to remove tumours, and chemotherapy (medicines for treating cancer) was used for cancers caused by the condition.

Selumetinib blocks enzymes called MEK1/2 which are involved in stimulating cells to grow. MEK1/2 are overactive in certain types of cancer, which makes cells grow uncontrollably. By blocking these enzymes, the medicine is expected to slow down growth of the tumour cells in neurofibromatosis type 1.

The effects of selumetinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with selumetinib in patients with neurofibromatosis type 1 were ongoing.

At the time of submission, selumetinib was not authorised anywhere in the EU for neurofibromatosis type 1. Orphan designation of the medicine 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 21 June 2018 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.