EU/3/20/2270: Orphan designation for the treatment of pyruvate kinase deficiency

Pyruvate kinase deficiency is an inherited disease that affects red blood cells, which carry oxygen to the body’s tissues and organs. It is caused by mutations (changes) in the gene for making an enzyme called pyruvate kinase, which is essential for the normal function of red blood cells. This results in a lack of functioning enzyme and reduced lifespan and early breakdown of these cells in the blood (haemolytic anaemia). Symptoms can include very pale skin, yellowing of the eyes and skin (jaundice), tiredness, shortness of breath (dyspnoea), enlarged spleen (splenomegaly) and heart problems. Anaemia and associated complications may be severe enough to require periodic blood transfusions.

Pyruvate kinase deficiency is a long-term debilitating disease because of its symptoms and the periodic blood transfusions. The condition can also be life threatening because the anaemia can worsen during pregnancy or during a viral infection.

At the time of designation, pyruvate kinase deficiency affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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, no satisfactory methods were authorised in the EU for the treatment of pyruvate kinase deficiency. Patients were given treatments to help alleviate their symptoms such as periodic red blood cell transfusions. In some patients, allogeneic stem-cell transplantation was used. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

In patients with pyruvate kinase deficiency, gene mutations cause the enzyme to be less stable and to work less effectively. This medicine is thought to work by stabilising the defective enzyme and helping it to work better, thus reducing 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 pyruvate kinase deficiency were ongoing.

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

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 19 March 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.