EU/3/18/2087

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 abnormal direct connections between arteries and veins, which are fragile, and can increase 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 approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 103,000 people¹, 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).

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.

Etamsylate acts in several ways to help stop bleeding. It increases the formation of proteins involved in blood clotting and decreases formation of prostacyclin I2, a type of fat that blocks clotting. Etamsylate also increases the activity of platelets (cell fragments in blood that help the blood to clot). The medicine is expected to be used as a nasal spray, which would reduce nosebleeds in patients with HHT.

The effects of etamsylate have been evaluated in experimental models.

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

At the time of submission, etamsylate was authorised in several European countries as tablets or solution for injection for prevention of bleeding.

At the time of submission, etamsylate 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 18 October 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.