EU/3/19/2156: Orphan designation for the treatment of propionic acidaemia

Propionic acidaemia is an inherited disease in which the body does not break down amino acids and fats properly. It is caused by mutations (changes) in genes responsible for producing an enzyme called propionyl CoA carboxylase. As a result, acids and ammonia build up in the blood and body tissues.

The condition usually appears shortly after birth and causes symptoms such as poor feeding, vomiting, reduced muscle strength, lack of energy, an enlarged heart and encephalopathy (a brain disorder).

Propionic acidaemia is a long-term debilitating and life-threatening disease because it can lead to fits, coma and heart failure.

At the time of designation, propionic acidaemia affected approximately 0.04 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

At the time of the orphan designation, Carbaglu was authorised in the EU for reducing high levels of ammonia in the blood of patients with propionic acidaemia. Other medicines were used to reduce production of acid in the gut. Patients were also advised to avoid further build-up of ammonia in the blood by eating a low-protein diet.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with propionic acidaemia, with laboratory data indicating that it could reduce the build-up of ammonia and reduce heart mass. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In patients with propionic acidaemia, the enzyme propionyl CoA carboxylase, which is involved in breaking down amino acids and fatty acids, does not work properly.

This medicine is made of genetic material contained in fatty particles. When injected into the patient, it is expected that the fatty particles deliver the genetic material into liver cells, making them able to produce working propionyl CoA carboxylase. This is expected to reduce patients' symptoms.

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for propionic acidaemia or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 21 March 2019, 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.