EU/3/08/577 - orphan designation for treatment of propionic acidaemia

carglumic acid

Overview

On 7 November 2008, orphan designation (EU/3/08/577) was granted by the European Commission to Orphan Europe SARL, France, for carglumic acid for the treatment of propionic acidaemia.

Carglumic acid for treatment of propionic acidaemia has been authorised in the EU as Carbaglu since 27 May 2011.

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in June 2021 at the end of the 10-year period of market exclusivity.

What is propionic acidaemia?

Propionic acidaemia is an inherited disease that usually appears in early infancy. It is caused by an abnormal gene. For a patient to develop this disease, he or she needs to have inherited one copy of the abnormal gene from each parent. This is called 'autosomal recessive' transmission. Patients with propionic acidaemia produce defective versions of an enzyme called propionyl-coenzyme A carboxylase, which is normally involved in the breakdown of parts of proteins and fats in the body. When these breakdown processes do not happen normally, it results in a build-up of propionic acid, ammonia and other toxic substances in the blood. This causes symptoms such as poor feeding, vomiting, hypotonia (reduced muscle tone causing floppiness), lethargy (lack of energy) and encephalopathy (problems with the brain).

The effects of propionic acidaemia can be life-threatening.

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

At the time of designation, methylmalonic acidaemia affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

What treatments are available?

Current treatments for propionic acidaemia aim to remove the ammonia that builds up in the blood. They include sodium benzoate, which is an ammonium scavenger (a substance that mops up ammonia in the blood). Patients can also avoid further build-up of ammonia in the blood by reducing their intake of nitrogen by eating a low-protein diet.

Carglumic acid could be of potential significant benefit for the treatment of propionic acidaemia, because it might act differently from other medicinal products. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Carglumic acid is very similar in structure to N-acetylglutamate, which activates an enzyme that breaks down ammonia. Carglumic acid therefore helps break down ammonia, reducing ammonia blood levels and its toxic effects. This is expected to relieve the symptoms of propionic acidaemia that are caused by high blood ammonia levels.

What is the stage of development of this medicine?

The effects of carglumic acid have not been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with propionic acidaemia had been initiated.

At the time of submission carglumic acid was not authorised anywhere in the world propionic acidaemia or designated as orphan medicinal product elsewhere for this condition.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 10 September 2008 recommending the granting of this designation.

Update: Carglumic acid (Carbaglu) was authorised in the EU on 27 May 2011 for treatment of hyperammonaemia due to methylmalonic acidaemia.

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 Community) 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/3/08/577: Public summary of positive opinion for orphan designation ofcarglumic acid for the treatment of propionic acidaemia

AdoptedReference Number: EMEA/COMP/481242/2008 Rev.1

Key facts

• Active substance:
  carglumic acid
• Medicine name:
  Carbaglu
• Intended use:
  Treatment of propionic acidaemia
• Orphan designation status:
  Expired
• EU designation number:
  EU/3/08/577
• Date of designation:
  07/11/2008
• Sponsor:

  Orphan Europe SARL; Immeuble Le Wilson; 70 Avenue du Général de Gaulle; F-92800 Puteaux; France; Tel. [phone]; Fax [phone]; E-mail: [e-mail]

Review of designation

During its meeting of 4-5 May 2011, the Committee for Orphan Medicinal Products (COMP) reviewed the designations for Carbaglu (carglumic acid) as an orphan medicinal product for the treatment of isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia.

The COMP assessed whether, at the time of addition of these new indications to the marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the conditions, and the existence of other satisfactory methods of treatment.

As other satisfactory methods of treatment for patients with these conditions are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designations of the medicine be maintained.