EU/3/20/2281: Orphan designation for the treatment of paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is a condition in which there is excessive breakdown of red blood cells (haemolysis), leading to the release into the urine of a large amount of haemoglobin (the protein in red blood cells that carries oxygen around the body). Because haemoglobin is red, the passing of red urine, particularly in the mornings, is usually the most obvious sign of the disease. Patients may also feel very tired and develop blood clots (thromboses) in veins and excess bleeding. PNH is a long-term debilitating and life-threatening condition due to its complications including abdominal pain, infection and kidney problems, and problems due to bleeding and blood clots.

At the time of designation, paroxysmal nocturnal haemoglobinuria affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 21,000 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).

^*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, Soliris (eculizumab) and Ultomiris (ravilizumab) were authorised in the EU for the treatment of PNH. Patients were also treated with hematopoietic stem cell transplantation, a procedure where the patient’s bone marrow is replaced to form new bone marrow that produces healthy cells. Other methods such as blood transfusions and treatment with medicines to prevent clotting were used to improve symptoms.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with paroxysmal nocturnal haemoglobinuria. This is because preliminary data support improved reduction of haemolysis, when the medicine is combined with available treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In PNH, red blood cells lack a protein on their surface which leaves them open to being broken down by the complement system, part of the immune system (the body's defences). The medicine blocks the activity of a protein called complement factor B. It is expected that this action will prevent breakdown of red blood cells and so reduce 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 paroxysmal nocturnal haemoglobinuria were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of paroxysmal nocturnal haemoglobinuria or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 23 April 2020, 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.