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Orphan designation

On 29 April 2009, orphan designation (EU/3/09/632) was granted by the European Commission to Amsterdam Molecular Therapeutics BV, the Netherlands, for adeno-associated viral vector containing porphobilinogen deaminase gene for the treatment of acute intermittent porphyria.

In July 2012, Amsterdam Molecular Therapeutics BV changed name to uniQure biopharma B.V.

What is acute intermittent porphyria?

Acute intermittent porphyria (AIP) is a genetic disease that affects the production of ‘haem’, a component of haemoglobin. Haemoglobin is the protein found in the red blood cells that carries oxygen around the body. Patients with AIP have attacks of abdominal (tummy) pain. They may also have symptoms affecting the nervous system, such as seizures (fits), depression, anxiety and psychosis (an altered sense of reality).

AIP is caused by abnormalities in the gene that is responsible for the production of a protein called porphobilinogen deaminase (PBGD). PBGD is involved in the production of haem by the liver. In patients with AIP, PBGD does not work properly. This causes accumulation of haem precursors (substances that are usually used to make haem) in the liver and in the blood. These substances are also found at high levels in the skin, which becomes oversensitive to light, and in the urine, which becomes red in colour.

AIP is a severe disease that is long-lasting and may be life-threatening because of its effects on the liver.

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

At the time of designation, AIP affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 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).

*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 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of designation, a medicine containing haem was authorised in some countries in the EU to treat acute attacks of AIP. In some cases, liver transplantation was used.

The sponsor has provided sufficient information to show that adeno-associated viral vector containing porphobilinogen deaminase gene might be of significant benefit for patients with AIP because it works in a different way to existing methods and could be an alternative long-term treatment for the disease. 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?

Adeno-associated viral vector containing porphobilinogen deaminase gene is a virus that contains normal copies of the PBGD gene. When injected into the liver, the virus carries the PBGD gene into the liver cells, where the gene is expected to enable the cells to start producing the PBGD protein. This will replace the defective protein, allowing the patients to start producing haem and reducing accumulation of haem precursors in the cells. This is expected to prevent attacks of AIP.

The type of virus used in this medicine (‘adeno-associated virus’) has been modified so that it does not cause disease in humans.

What is the stage of development of this medicine?

The effects of adeno-associated viral vector containing porphobilinogen deaminase gene have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with AIP had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for AIP 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 4 March 2009 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 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.

Key facts

Product details for <p>Adeno-associated viral vector containing porphobilinogen deaminase gene</p>
Active substanceAdeno-associated viral vector containing porphobilinogen deaminase gene
Medicine Name
Disease/conditionTreatment of acute intermittent porphyria
Date of decision29/04/2009
Orphan decision numberEU/3/09/632

Review of designation

Sponsor’s contact details

uniQure biopharma B.V.
Meibergdreef 61
1105 BA
The Netherlands
Tel. +31 20 566 7394
Fax +31 20 566 9272

Patient associations’ contact points

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.