EU/3/18/2096: Orphan designation for the treatment of anti-glomerular basement membrane disease

Anti–glomerular basement membrane disease is a disease in which the immune system (the body’s natural defences) produces abnormal antibodies against targets present in the glomerular basement membrane (GBM) found in the kidneys and the alveolar basement membrane in the lungs.

Patients with anti-GBM disease develop inflammation and bleeding in the lung and a kidney disease called glomerulonephritis, in which the small filtering units in the kidneys are damaged.

Anti-GBM disease is a long-term debilitating and life-threatening disease that can lead to lung problems and kidney failure.

At the time of orphan designation, anti-GBM disease affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,000 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).

At the time of orphan designation, treatments for anti-GBM disease included medicines to reduce inflammation, such as corticosteroids and cyclophosphamide, as well as plasma exchange, a procedure to remove antibodies from plasma (the liquid part of the blood) by replacing the patient’s plasma with plasma from a donor. 

The sponsor has provided sufficient information to show that imlifidase might be of significant benefit for patients with anti-GBM disease because preliminary data showed that patients treated with the medicine had improved kidney function compared with standard of care.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Imlifidase is made of an enzyme derived from the bacterium Streptococcus pyogenes. This enzyme breaks down certain types of antibodies including the abnormal antibodies produced in anti-GBM disease. By breaking down the abnormal antibodies, the medicine is expected to reduce inflammation and improve 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 anti-GBM disease were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for anti-GBM disease. Orphan designation of the medicine had been granted in the United States for anti-GBM disease. 

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.