On 12 December 2017, orphan designation (EU/3/17/1946) was granted by the European Commission to FGK Representative Service GmbH, Germany, for (2S,4R)-1-(2-(3-acetyl-5-(2-methylpyrimidine-5-yl)-1H-indazol-1-yl)acetyl)-N-(6-bromopyridine-2-yl)-4-fluoropyrrolidine-2-carboxamide (also known as ACH-0144471) for the treatment of paroxysmal nocturnal haemoglobinuria.
The sponsorship was transferred to Alexion Europe S.A.S. France, in June 2020.
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 found in red blood cells that carries oxygen around the body). Because of the red colour of haemoglobin, the passing of red urine, particularly in the mornings, is usually the most obvious sign of the disease. Patients may also experience problems related to blood clotting.
The condition is caused by the lack of certain proteins on the surface of the red blood cells which normally protect them from being destroyed by the immune system (the body's natural defences).
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, PNH affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 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).
1Disclaimer: 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 515,700,000 (Eurostat 2017).
At the time of designation, Soliris (eculizumab) was authorised in the EU for the treatment of PNH. Bone marrow transplantation to replace the defective red blood cells was another therapy available to patients. Other methods such as blood transfusions and treatment with medicines to prevent clotting were used in some patients to improve symptoms.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with PNH. This is because preliminary data have shown that the medicine can reduce the number of transfusions in a form of the disease associated with another condition (aplastic anaemia) that cannot be treated with eculizumab.
This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
In patients with PNH, proteins of the immune system called complement proteins damage the patients' own blood cells.
The medicine blocks a complement protein called factor D. Blocking this protein is expected to help prevent complement proteins from damaging blood cells, thereby relieving 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 PNH were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for PNH 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 31 October 2017 recommending the granting of this designation.
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.
Alexion Europe S.A.S.
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: