EU/3/18/2074 - orphan designation for treatment of mastocytosis

Avapritinib

Overview

On 26 October 2018, orphan designation (EU/3/18/2074) was granted by the European Commission to PhaRA bvba, Belgium, for avapritinib (also known as BLU-285) for the treatment of mastocytosis.

The medicinal product has been authorised in the EU as Ayvakyt since 24 March 2022.

What is mastocytosis?

Mastocytosis is a group of disorders in which there are too many mast cells (a type of white blood cell) in various organs in the body. These cells release large amounts of histamine and other substances into the blood, causing symptoms such as a skin rash, itchy skin and hot flushes.

In children, the disorder usually only affects the skin ('cutaneous mastocytosis') and causes a red and itchy rash, which may disappear on its own. In some adults, the disorder progresses into 'systemic mastocytosis', in which the mast cells infiltrate organs, such as the intestine, the liver, the spleen and the bone marrow. This causes various symptoms such as palpitations, fainting, bone pain, tiredness, weight loss, diarrhoea, nausea (feeling sick), vomiting and stomach ache.

Mastocytosis is a condition that is debilitating in the long term and may be life threatening in those patients who develop the systemic form of the disorder.

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

At the time of designation, mastocytosis affected approximately 3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 155,000 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 517,400,000 (Eurostat 2018).

What treatments are available?

At the time of designation, the medicine Rydapt (midostaurin) was authorised in the EU for the treatment of systemic mastocytosis. Treatments to relieve some of the symptoms of mastocytosis, including antihistamines such as cimetidine or famotidine, were also available.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with mastocytosis because preliminary results showed that more patients responded to treatment with avapritinib than with midostaurin. 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?

Avapritinib is a tyrosine kinase inhibitor. This means that it blocks the action of certain enzymes known as tyrosine kinases. These enzymes, which can be found on the surface of mast cells, are involved in stimulating the growth of mast cells in mastocytosis. By blocking these enzymes, avapritinib is expected to control the growth of mast cells, slowing down the progression of mastocytosis.

What is the stage of development of this medicine?

The effects of avapritinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with avapritinib in patients with mastocytosis were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 September 2018 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/3/18/2074: Public summary of opinion on orphan designation: Avapritinib for the treatment of mastocytosis

AdoptedReference Number: EMA/674141/2018

Key facts

• Active substance:
  Avapritinib
• Intended use:
  Treatment of mastocytosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2074
• Date of designation:
  26/10/2018
• Sponsor:

  Blueprint Medicines (Netherlands) B.V.;

Review of designation

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

More information is available in the Ayvakyt : Orphan maintenance assessment report (post authorisation) (X-04-G).