EU/3/16/1670 - orphan designation for treatment of Langerhans' cell histiocytosis

vemurafenib

Overview

On 30 May 2016, orphan designation (EU/3/16/1670) was granted by the European Commission to Groupe d'étude des histiocytoses, Hôpital Trousseau, France, for vemurafenib for treatment of Langerhans' cell histiocytosis.

What is Langerhans' cell histiocytosis?

Langerhans' cell histiocytosis is a disease in which immune cells known as Langerhans' cells grow quickly and accumulate in various tissues in the body including in bone, skin, liver, spleen, lungs, pituitary gland (gland located at the base of the brain) and the central nervous system (brain and spinal cord).

Langerhans' cell histiocytosis occurs mainly in childhood and the features vary depending on the parts of the body affected. Common features include bone pain and swelling, skin rash, breathing problems, liver problems and reduced blood cells.

Langerhans' cell histiocytosis is a life-threatening and debilitating condition that can lead to various serious complications depending on the organ affected.

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

At the time of designation, Langerhans' cell histiocytosis 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).

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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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of orphan designation, the main treatment for Langerhans' cell histiocytosis was chemotherapy which usually included vinblastine (authorised to treat histiocytosis, a group of conditions that includes Langerhans' cell histiocytosis). Treatment guidelines also recommended the use of other medicines although not authorised for this condition.

The sponsor has provided sufficient information to show that vemurafenib might be of significant benefit for patients with Langerhans' cell histiocytosis. Published clinical data have shown vemurafenib successfully treating patients whose condition did not improve with standard treatment. 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?

Around half of the cases of Langerhans' cell histiocytosis are due to a mutation (change) in the BRAF gene, called the BRAF V600E mutation. This mutation results in the production of an abnormal BRAF protein which makes Langerhans' cells grow and divide quickly. Vemurafenib is expected to work by attaching to and blocking the abnormal BRAF protein thereby slowing down the growth and spread of the Langerhans cells.

What is the stage of development of this medicine?

The effects of vemurafenib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, the sponsor had not started clinical trials with vemurafenib in patients with Langerhans' cell histiocytosis.

At the time of submission, vemurafenib was authorised in the EU for unresectable or metastatic melanoma (a skin cancer) in patients with the BRAF V600E mutation.

At the time of submission, vemurafenib was not authorised anywhere in the EU for Langerhans' cell histiocytosis 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 21 April 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/3/16/1670: Public summary of opinion on orphan designation: Vemurafenib for treatment of Langerhans’ cell histiocytosis

Adopted Reference Number: EMA/COMP/313647/2016

Key facts

• Active substance:
  vemurafenib
• Intended use:
  Treatment of Langerhans' cell histiocytosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1670
• Date of designation:
  30/05/2016
• Sponsor:

  Groupe d'étude des histiocytoses; Hôpital Trousseau; 26 avenue du Dr Netter; Paris 75012 ; France; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.