EU/3/16/1784: Orphan designation for the treatment of 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 disability if left untreated.

At the time of designation, hyperphenylalaninaemia affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 people¹, 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).

¹Disclaimer: 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).

At the time of designation, the medicine Kuvan (sapropterin) was authorised in the EU for the treatment of hyperphenylalaninaemia of certain causes. In addition, patients were advised to follow a lifelong strict diet low in phenylalanine-containing foods (which include meat, fish, eggs, nuts, legumes and corn) to reduce phenylalanine intake.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with hyperphenylalaninaemia because experimental results suggest it could be useful to patients in whom the existing approved medicine cannot be used. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine consists of particles of a long plastic-like substance (a polymer) that is not digested or absorbed by the body. The polymer has been designed to attach selectively to phenylalanine or protein fragments that contain phenylalanine. When the medicine is given with food, it is expected to attach to the phenylalanine from food proteins as they are broken down in the gut, preventing the amino acid from being absorbed. The medicine and its attached phenylalanine will then pass out of the body in the stools, helping to keep levels of phenylalanine in the body from rising.

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

No clinical trials with the medicine in patients with hyperphenylalaninaemia had been started.

At the time of submission, the medicine 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 6 October 2016 recommending the granting of this designation.

• 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.