EU/3/14/1374 - orphan designation for treatment of Gaucher disease

(3S)-1-azabicyclo[2.2.2]oct-3-yl{2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl}carbaNmate (venglustat)

Overview

This medicine is now known as venglustat.

On 19 November 2014, orphan designation (EU/3/14/1374) was granted by the European Commission to Genzyme Europe BV, the Netherlands, for (3S)-1-azabicyclo[2.2.2]oct-3-yl{2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl}carbamate for the treatment of Gaucher disease.

The sponsor’s address was updated in December 2018.

What is Gaucher disease?

Gaucher disease is an inherited disorder that is caused by the lack of an enzyme called glucocerebrosidase. This enzyme normally breaks down a fatty waste product called glucocerebroside. Without the enzyme, glucocerebroside builds up in the body, typically in the liver, spleen and bone marrow. This causes a wide range of symptoms, including anaemia (low red blood cell counts), tiredness, easy bruising and a tendency to bleed, an enlarged spleen and liver, and bone pain and fractures. Some severe forms of the disease affecting children also involve the brain, which may cause problems such as abnormal eye and head movements and seizures (fits).

Gaucher disease is a long-term debilitating and life-threatening disease that is associated with a reduced life expectancy if left untreated.

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

At the time of designation Gaucher disease 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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, three medicines (imiglucerase, miglustat and velaglucerase alfa) were authorised for the treatment of Gaucher disease in the EU. Imiglucerase and velaglucerase alfa are 'enzyme replacement therapies' that work by replacing the missing enzyme. Miglustat blocks the production of glucocerebroside and is used in patients who cannot receive enzyme replacement therapy.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with Gaucher disease because early studies in experimental models have reported that the medicine is able to cross from the blood into brain cells, which may be beneficial for patients with the form of the disease affecting the brain. These assumptions 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?

This medicine is expected to work in patients with Gaucher disease by blocking the action of an enzyme (glucosylceramide synthase) involved in the production of glucocerebroside. This is expected to help reduce glucocerebroside production and so help limit the extent of the damage and improve the symptoms of the disease. Because the medicine is thought to cross the 'blood-brain barrier' (a membrane barrier that prevents substances from the blood entering the brain), it is expected to be also able to reach cells in the brain where glucocerebroside accumulates in severe forms 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, clinical trials with the medicine in patients with Gaucher disease had not started.

At the time of submission, the medicine was not authorised anywhere in the EU for Gaucher 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 9 October 2014 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/3/14/1374: Public summary of opinion on orphan designation: (3S)-1-azabicyclo[2.2.2]oct-3-yl{2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl}carbamate for the treatment of Gaucher disease

Adopted Reference Number: EMA/COMP/645261/2014

Key facts

• Active substance:
  (3S)-1-azabicyclo[2.2.2]oct-3-yl{2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl}carbaNmate (venglustat)
• Intended use:
  Treatment of Gaucher disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/14/1374
• Date of designation:
  19/11/2014
• Sponsor:

  Sanofi B.V.

Review of designation

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