EU/3/14/1373: Orphan designation for the treatment of granulomatosis with polyangiitis

Granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) is a type of inflammation of small to medium-sized arteries and veins, characterised by 'granulomas' (clumping of white blood cells into small granular lumps that result in inflammation). Often the small blood vessels (capillaries) of the nose, throat, lungs and kidneys are affected, which causes symptoms such as itchy, runny nose, breathing problems and reduced kidney function or kidney failure. Other symptoms of the disease include fever, skin rash, muscle and joint pain. Although its causes are not well understood, granulomatosis with polyangiitis is an auto-immune disease, a disease which is caused by the body's immune system attacking normal tissue and which causes inflammation.

Granulomatosis with polyangiitis is a long-term debilitating and life-threatening condition, due to the damage to the kidneys and lungs which may cause kidney and respiratory failure.

At the time of designation granulomatosis with polyangiitis affected approximately 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 82,000 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, the medicine rituximab, in combination with corticosteroids, was authorised for granulomatosis with polyangiitis in the EU. Several other medicines, including cyclophosphamide with corticosteroids, were also used. Patients with severely impaired kidney function might be given plasmapheresis (a process similar to kidney dialysis in which the liquid part of the blood, or plasma, is separated from the cells in order to remove antibodies).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with granulomatosis with polyangiitis because early studies show that it could improve kidney function in patients with the condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine blocks a receptor called 'complement 5a receptor' (C5aR), which is normally activated by C5a, one of a group of proteins in the blood ('the complement system') that form part of the immune system.

When C5a attaches to C5aR it attracts and activates certain immune cells called neutrophils, which are thought to contribute to the inflammation of small blood vessels in granulomatosis with polyangiitis. By blocking C5aR, the medicine is expected to reduce inflammation of blood vessels, thus improving the symptoms of the disease.

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 granulomatosis with polyangiitis were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for granulomatosis with polyangiitis. Orphan designation for this medicine had been granted in the United States for the treatment of this condition.

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.