EU/3/20/2324: Orphan designation for the treatment of von Hippel-Lindau disease

Von Hippel-Lindau disease is a genetic disease characterised by growth of mostly benign but also cancerous tumours in many organs of the body, including in the kidneys, pancreas, adrenal glands and inner ear, as well as abnormal growth of blood vessels in the eye, brain and spinal cord.

The disease is caused by a defect in the VHL gene which is responsible for the production of a protein that prevents tumour formation. In patients with von Hippel-Lindau disease, the defective gene cannot produce sufficient protein that works properly, leading to the development of tumours.

Von Hippel-Lindau disease is a long-term debilitating and life-threatening disease due to the complications caused by the various tumours that can have wide-ranging effects on the body.

At the time of designation, von Hippel-Lindau disease affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 16,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, no satisfactory methods were authorised in the EU for treating von Hippel-Lindau disease. Patients were mainly treated with surgery to remove tumours in the affected organs and with laser therapy to treat eye symptoms.

The medicine blocks the activity of a protein called HIF-2α, which accumulates when the oxygen levels in cells are low. HIF-2α promotes cell survival, cell growth and formation of new blood vessels. HIF-2α levels are raised in patients with von Hippel-Lindau disease (even when oxygen levels are normal). Therefore, by blocking the activity of HIF-2α, it is expected that the medicine will slow down worsening of the disease and improve symptoms.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with von Hippel-Lindau disease were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of von Hippel-Lindau disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 16 July 2020, 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.