EU/3/14/1367: Orphan designation for the treatment of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT, also known as Rendu-Osler-Weber syndrome) is a genetic disease that causes abnormalities in the capillaries (small blood vessels that connect arteries with veins). 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 spontaneous and 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 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 102,000 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 511,100,000 (Eurostat 2014).

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.

Patients with HHT normally have a mutation (defect) in one of two genes responsible for the production of two proteins known as ALK1 (activin receptor-like kinase type I) and ENG (endoglin). These proteins are involved in angiogenesis (formation of new blood vessels) and wound healing. Bazedoxifene mimics the effects of the hormone oestrogen, which stimulates the genes for ALK1 and ENG to increase the production of these proteins. By increasing production of ALK1 and ENG, the medicine is expected to relieve the symptoms of bleeding in HHT.

At the time of submission of the application for orphan designation, the evaluation of the effects of bazedoxifene acetate in experimental models was ongoing.

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 the medicine was not authorised anywhere in the EU for HHT or designated as an orphan medicinal product elsewhere for this condition. Bazedoxifene is authorised in the EU for the treatment of osteoporosis in women who have been through the menopause.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 2014 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.