EU/3/16/1769 - orphan designation for treatment of sickle cell disease

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (voxelotor)

Overview

On 18 November 2016, orphan designation (EU/3/16/1769) was granted by the European Commission to SynteractHCR Deutschland GmbH, Germany, for 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (also known as GBT440) for the treatment of sickle cell disease.

This medicine is now known as voxelotor.

The sponsorship was transferred to Global Blood Therapeutics Netherlands B.V., the Netherlands in January 2021.

Voxelotor has been authorised in the EU as Oxbryta since 14 February 2022.

What is sickle cell disease?

Sickle cell disease is a genetic disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped (like a sickle). The change in shape is caused by the presence of an abnormal form of haemoglobin, the protein in red blood cells that carries oxygen around the body. In patients with sickle cell disease, the abnormal red blood cells attach to other blood cells and to the walls of blood vessels and block them, restricting the flow of oxygen-rich blood to the internal organs such as the heart, lungs and spleen. Because the abnormal red blood cells have a shorter life span, they release haemoglobin into the blood circulation rather than carrying it to the internal organs where it is needed. As a result, patients experience severe pain as well as repeated infections and anaemia (low red-blood-cell counts).

Sickle cell disease is a severe disease that is long-lasting and may be life-threatening because of damage to the heart and the lungs, anaemia and infections.

What is the estimated number of patients affected by the condition?

At the time of designation, sickle cell disease affected approximately 3.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 164,000 people¹, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide. The main treatment for sickle cell disease was blood transfusion. This was usually combined with 'iron chelators' (medicines used to treat iron overload, high iron levels in the body caused by repeated blood transfusions), which are necessary in patients with long-term anaemias such as sickle cell disease. In some cases, haematopoietic (blood) stem cell transplantation was used. This is a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor to form new bone marrow that produces healthy blood cells containing normal haemoglobin.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with sickle cell disease because early studies showed that the medicine decreases the number of sickle-shaped red blood cells and reduces haemolysis (the breakdown of red blood cells). This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

In sickle cell disease, sickling of the red blood cells occurs when the abnormal haemoglobin releases its oxygen and then clumps together to form rigid chains that make the cells change shape.

This medicine is expected to work by increasing the ability of the abnormal haemoglobin to take up and hold oxygen. With more oxygen attached to the haemoglobin, it is expected that the haemoglobin will be less likely to clump together and cause sickling. The number of sickle-shaped red blood cells will subsequently fall and the patient's symptoms should start to improve.

What is the stage of development of this medicine?

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 sickle cell disease were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/16/1769: Public summary of positive opinion for orphan designation of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde for the treatment of sickle cell disease

Key facts

• Active substance:
  2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (voxelotor)
• Intended use:
  Treatment of sickle cell disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1769
• Date of designation:
  18/11/2016
• Sponsor:

  Pfizer Europe MA EEIG;

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Oxbryta at the time of marketing authorisation, and confirmed that the orphan designation should be maintained.

More information is available in the .