EU/3/17/1846

On 27 February 2017, orphan designation (EU/3/17/1846) was granted by the European Commission to Groupe d’étude des histiocytoses, France, for vemurafenib for the treatment of Erdheim-Chester disease.

What is Erdheim-Chester disease?

Erdheim-Chester disease is a condition in which cells of the immune (defence) system known as histiocytes build up in various tissues in the body including bones, eyes, kidneys, skin, brain, lungs and heart. This can lead to serious damage to organs, bone pain, bulging eyes, nerve damage affecting eye control, reduced mental function and diabetes insipidus (a condition where the body cannot regulate water and urine properly). Most patients are diagnosed with Erdheim-Chester disease after the age of 40 years. The severity of the symptoms varies from patient to patient.

Erdheim-Chester disease is a debilitating and life-threating condition because it can lead to serious complications.

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

At the time of designation, Erdheim-Chester disease affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 people*, 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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*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, no satisfactory methods were authorised in the EU for the treatment of Erdheim-Chester disease. Patients were treated with cytotoxic agents (medicines that kill cells), interferon alfa (which works on the immune system), corticosteroids and autologous haematopoietic stem cell transplantation (in which the bone marrow is cleared of cells and replaced with the patient’s own stem cells).

How is this medicine expected to work?

A proportion of cases of Erdheim-Chester disease are thought to result from a mutation (change) in the BRAF gene, called the BRAF V600E mutation. This mutation leads to the production of an abnormal BRAF protein which causes histiocytes to build up in tissues and leads to the symptoms. Vemurafenib works by blocking the abnormal BRAF protein, and by doing this it is expected to slow down the build-up of histiocytes and so help to control the complications of Erdheim-Chester disease.

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, clinical trials with vemurafenib in patients with Erdheim-Chester disease were ongoing.

At the time of submission, vemurafenib (as Zelboraf tablets) was authorised in the EU for certain types of melanoma (a skin cancer) associated with the BRAF V600 mutation.

At the time of submission, vemurafenib was not authorised anywhere in the EU for Erdheim-Chester disease. Orphan designation of the medicine had been granted in the United States for Erdheim-Chester disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 January 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.

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