EU/3/17/1970 - orphan designation for treatment of sickle cell disease

sirolimus

Overview

On 17 January 2018, orphan designation (EU/3/17/1970) was granted by the European Commission to Rare Partners srl Impresa Sociale, Italy, for sirolimus for the treatment of sickle cell disease.

The sponsor’s address was updated in May 2020.

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 life-long disease 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 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 134,000 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).

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*Disclaimer: 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).

What treatments are available?

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide (hydroxyurea). The main treatment for sickle cell disease was blood transfusion. This was usually combined with 'iron chelators' (medicines used to reduce high iron levels in the body resulting from repeated blood transfusions). 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 preliminary results suggest that combining sirolimus with the approved treatment, hydroxycarbamide, could improve the lifespan and function of red blood cells more than either medicine alone. 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?

Sirolimus has been approved in the EU for many years to reduce the activity of the immune (defence) system and prevent the body from rejecting a newly transplanted kidney. Its action in sickle cell disease is thought to be due to its ability to encourage the production of an alternative form of haemoglobin, fetal haemoglobin, that works in the same way as normal haemoglobin and does not make cells become sickle-shaped. This is expected to improve the ability of the red blood cells to carry oxygen around the body and to reduce the damaging effects of sickle-shaped cells, helping to control the symptoms of the disease.

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, no clinical trials with sirolimus in patients with sickle cell disease had been started.

At the time of submission, sirolimus was not authorised anywhere in the EU for sickle cell disease 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 7 December 2017 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/3/17/1970: Public summary of opinion on orphan designation: Sirolimus for the treatment of sickle cell disease

Adopted Reference Number: EMA/826628/2017

Key facts

• Active substance:
  sirolimus
• Intended use:
  Treatment of sickle cell disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1970
• Date of designation:
  17/01/2018
• Sponsor:

  Rare Partners srl Impresa Sociale; Via Giovanni Boccaccio 20; 20123 Milano; Italy; Tel. [phone]; Fax [phone]; E-mail: [e-mail]