EU/3/17/1845: Orphan designation for the treatment of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT, also known as Rendu-Osler-Weber syndrome) is a genetic disease in which the capillaries (tiny blood vessels that connect arteries with veins) do not develop properly. This results in direct connections between arteries and veins, which are fragile, increasing the risk of bleeding. The most common symptoms of the disease are frequent nosebleeds and red spots on the skin, particularly on the face and hands and in the mouth. Bleeding can also occur in the stomach, gut, brain, liver and lungs, and often leads to anaemia (low red blood cell counts).

HHT is a long-term debilitating disease that may be life threatening because of its complications, such as internal bleeding and effects on organs such as the gut, brain, liver and lungs.

At the time of designation, HHT affected not more than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 103,000 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, no satisfactory methods were authorised in the EU for the treatment of HHT. Different methods were used to control bleeding, which depend mainly on where in the body it occurred. For nosebleeds, patients used nasal humidifiers and lubricants. Laser treatment and surgery were used to stop internal bleeding. In patients with severe liver problems, liver transplantation was performed. When bleeding caused anaemia, patients were given iron supplements and blood transfusions.

In HHT, thalidomide is thought to work on mural cells (cells in the blood vessel wall) by increasing their number and their ability to support blood vessels. This leads to blood vessels becoming stronger. These effects of thalidomide are expected to reduce bleeding, especially nose bleeds, in patients with HHT.

The company provided data from the published literature on the effects of thalidomide in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with HHT were ongoing.

At the time of submission, thalidomide was authorised in the EU for the treatment of multiple myeloma.

At the time of submission, the medicine was not authorised anywhere in the EU for HHT 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 19 January 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.