EU/3/16/1818 - orphan designation for treatment of acute liver failure

human hepatoma cell line HepaRG in bioartificial liver

Overview

On 12 January 2017, orphan designation (EU/3/16/1818) was granted by the European Commission to Hep-Art Medical Devices BV, the Netherlands, for human hepatoma cell line HepaRG in bioartificial liver (also known as HepaRG-AMC-BAL) 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 0.06 in 10,000 people in the European Union (EU). This was equivalent to a total of around 3,000 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 this product might be of significant benefit for patients with acute liver failure because early results suggest it could improve survival in patients waiting for a liver transplant. 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?

The product consists of a medical device that contains cultured liver cells. These cells are attached to multiple layers of a supporting structure. The device is expected to act as a temporary 'artificial liver' outside the patient's body.

The patient's blood is continuously drawn from a vein, and the plasma (the liquid part of the blood) is separated and passed between the supporting layers in the device. Toxins that affect the brain in patients with liver failure, such as ammonia, are converted to less toxic substances by the liver cells in the device in the same way as in a normal liver. The plasma is then recombined with the other parts of the blood and the blood is returned to the patient. In this way, the product is expected to help support the patient's own liver by carrying out some of its essential functions, thereby relieving the symptoms of acute liver failure until a transplant can be obtained. This support may also permit some improvement in the function of the patient's damaged liver.

What is the stage of development of this medicine?

The effects of the product have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with this product in patients with acute liver failure had been started.

At the time of submission, the product 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 8 December 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/3/16/1818: Public summary of opinion on orphan designation: Human hepatoma cell line HepaRG in bioartificial liver for the treatment of acute liver failure

Adopted Reference Number: EMA/3424/2017

Key facts

• Active substance:
  human hepatoma cell line HepaRG in bioartificial liver
• Medicine name:
  -
• Intended use:
  Treatment of acute liver failure
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1818
• Date of designation:
  12/01/2017
• Sponsor:

  Hep-Art Medical Devices BV; Meibergdreef 45; 1105 BA Amsterdam; The Netherlands; Tel. [phone]; E-mail: [e-mail]

Review of designation

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