EU/3/16/1675 - orphan designation for treatment of acute liver failure

citric acid monohydrate

Overview

On 27 June 2016, orphan designation (EU/3/16/1675) was granted by the European Commission to CATS Consultants GmbH, Germany, for citric acid monohydrate for the treatment of acute liver failure.

What is acute liver failure?

Acute liver failure is the sudden loss of normal liver function in a patient with a previously normal liver and without evidence of chronic (long-term) liver disease.

The most common first sign of liver failure is jaundice (yellowing of the skin). Acute liver failure brings serious complications such as excessive bleeding due to impaired blood clotting, swelling around the brain, convulsions (fits) and coma.

The most common causes of acute liver failure are viral hepatitis (an infectious disease that affects the liver), overdose of medicines such as paracetamol or consumption of toxic substances such as poisonous mushrooms.

Acute liver failure is a life-threatening disease because of its damaging effects on the liver, brain and other organs.

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

At the time of designation, acute liver failure affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 designation, the main treatment option for acute liver failure was liver transplantation. Patients with acute liver failure caused by paracetamol overdose were treated with N-acetylcysteine.

The sponsor has provided sufficient information to show that citric acid monohydrate might be of significant benefit for patients with acute liver failure because early laboratory studies indicate that it may prolong survival of patients until a liver transplant is possible. 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?

One function of the liver is to transform ammonia into urea which is then harmlessly eliminated in the urine. When the liver fails, it cannot transform ammonia into urea. The ammonia then builds up in the blood and the brain causing many of the symptoms of acute liver failure.

This medicine is a fluid made of microscopic fat particles, called liposomes, containing a solution of citric acid. The fluid is to be injected into the space inside the abdomen (belly). Ammonia is then expected to pass from the blood vessels lining the abdomen into the liposomes, where it is trapped and removed from the body when the fluid is drained out of the abdomen. Citric acid may also help to eliminate other toxic substances.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of this medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with acute liver failure had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for acute liver failure 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 19 May 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/3/16/1675: Public summary of opinion on orphan designation: Citric acid monohydrate for the treatment of acute liver failure

Adopted Reference Number: EMA/COMP/384853/2016

Key facts

• Active substance:
  citric acid monohydrate
• Intended use:
  Treatment of acute liver failure
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1675
• Date of designation:
  27/06/2016
• Sponsor:

  Genfit; Parc Eurasante Lille Metropole; 885 Avenue Eugene Avinee; 59120 Loos; France; Tel. [phone]; E-mail: [e-mail]