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Orphan designation

This medicine is now known as pegvaliase.

On 28 January 2010, orphan designation (EU/3/09/708) was granted by the European Commission to BioMarin Europe Ltd, United Kingdom, for pegylated recombinant phenylalanine ammonia lyase for the treatment of hyperphenylalaninaemia.

The sponsorship was transferred to BioMarin International Limited, Ireland, in August 2016.

What is hyperphenylalaninaemia?

Hyperphenylalaninaemia is high levels of phenylalanine in the blood. Phenylalanine is an amino acid, one of the building blocks of proteins, and comes from the diet. Hyperphenylalaninaemia mainly occurs in patients with a genetic disorder called phenylketonuria (PKU). Patients with this disorder cannot convert phenylalanine into tyrosine (another amino acid). This causes a build-up of phenylalanine in the blood, which causes problems with the brain and nervous system.

Hyperphenylalaninaemia is a long-term debilitating disease that leads to mental retardation if left untreated.

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

At the time of designation, hyperphenylalaninaemia affected approximately 1.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 86,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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. This represents a population of 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of designation, one product was authorised in the EU for the treatment of hyperphenylalaninaemia. In addition, patients were advised to follow a lifelong strict diet low in phenylalanine-containing foods (such as meat, fish, eggs, nuts, legumes and corn) to reduce phenylalanine intake.

The sponsor has provided sufficient information to show that pegylated recombinant phenylalanine ammonia lyase might be of significant benefit for patients with hyperphenylalaninaemia because it works in a different way to existing treatment and because early studies indicate that it might improve the outcome of patients who do not respond to existing treatment. 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?

Hyperphenylalaninaemia is mainly caused by the lack of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine into tyrosine.

Pegylated recombinant phenylalanine ammonia lyase is a bacterial enzyme that can break down phenylalanine in a similar way to PAH. In the body, it is expected to replace the missing PAH. This is expected to stop the accumulation of phenylalanine in the body, relieving the symptoms of the disease.

Pegylated recombinant phenylalanine ammonia lyase is made by a method known as ‘recombinant DNA technology’: it is made by a bacterium that has received a gene (DNA) that makes it able to produce phenylalanine ammonia lyase. The enzyme has also been modified by a process called ‘pegylation’, meaning that it has been attached to a chemical called polyethylene glycol.

What is the stage of development of this medicine?

The effects of pegylated recombinant phenylalanine ammonia lyase have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with hyperphenylalaninaemia were ongoing.

At the time of submission, pegylated recombinant phenylalanine ammonia lyase was not authorised anywhere in the EU for hyperphenylalaninaemia 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 5 November 2009recommending 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>Pegylated recombinant phenylalanine ammonia lyase (pegvaliase)</p>
Active substancePegylated recombinant phenylalanine ammonia lyase (pegvaliase)
Medicine Name
Disease/conditionTreatment of hyperphenylalaninaemia
Date of decision28/01/2010
Orphan decision numberEU/3/09/708

Review of designation

Sponsor’s contact details

BioMarin International Limited
County Cork
Tel. +353 2 15 00 86 00

Patients' organisations

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.