EU/3/19/2183 - orphan designation for treatment of WHIM syndrome

Mavorixafor

Overview

On 25 July 2019, orphan designation EU/3/19/2183 was granted by the European Commission to Voisin Consulting S.A.R.L., France, for mavorixafor for the treatment of WHIM syndrome.

In October 2021, Voisin Consulting S.A.R.L. changed name to Voisin Consulting Life Sciences.

What is WHIM syndrome?

WHIM syndrome is a hereditary condition in which the immune system (the body’s natural defences) does not work properly, making patients more susceptible to bacterial and viral infections.

WHIM stands for warts (skin growths), hypogammaglobulinemia (low level of antibodies), infections and myelokathexis (a condition where immune cells are trapped in the bone marrow preventing them from fighting infections).

Patients with the condition may have warts in the hands, feet and anogenital area caused by viral infections, and are at risk of recurrent bacterial infections such as ear infections and pneumonia, due to low levels of neutrophils and lymphocytes (types of white blood cells) and of antibodies produced by the white bloods cells to fight infections.

WHIM syndrome is a long-term debilitating and life-threatening condition because of the recurrent infections and the increased risk of developing viral-associated cancer over time.

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

At the time of designation, WHIM syndrome affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 500 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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU to treat WHIM syndrome. Patients were given treatment to relieve the symptoms of the condition, including granulocyte-colony stimulating factor which stimulates the bone marrow to produce neutrophils and immunoglobulins (proteins naturally found in the blood that help the body to fight infections and other diseases).

How is this medicine expected to work?

Patients with WHIM syndrome have mutations (changes) in the gene for the CXCR4 receptor, which plays a role in the movement of blood cells into and from the bone marrow (where blood cells are produced). Because of these mutations, the CXCR4 receptor is hyperactive and, as a consequence, blood cells (particularly neutrophils) are retained in the bone marrow, leading to low levels of neutrophils in the blood.

Mavorixafor is expected to reduce the activity of the CXCR4 receptor and allow neutrophils to be released from the bone marrow into the blood stream. This increases the levels of neutrophils in the blood thereby helping the body to fight infections.

What is the stage of development of this medicine?

The effects of mavorixafor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with mavorixafor in patients with WHIM syndrome were ongoing.

At the time of submission, mavorixafor was not authorised anywhere in the EU for the treatment of WHIM syndrome. Orphan designation of mavorixafor had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 June 2019, 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/3/19/2183: Public summary of opinion on orphan designation: Mavorixafor for the treatment of WHIM syndrome

Reference Number: EMADOC-628903358-1133

Key facts

• Active substance:
  Mavorixafor
• Intended use:
  Treatment of WHIM syndrome
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2183
• Date of designation:
  25/07/2019
• Sponsor:

  X4 Pharmaceuticals (Austria) GmbH

Review of designation

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