EU/3/16/1779: Orphan designation for the treatment of fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva is a genetic condition which causes abnormal formation of bone in the muscles, tendons and ligaments. It is caused by a mutation (change) in the gene for 'ACVR1', a receptor involved in the formation of bone and cartilage. The mutation results in the receptor not working as it should, causing the formation of unwanted bone in muscles and joints throughout the body.

Patients have episodes of pain, inflammation and swelling ('flare-ups'), often triggered by minor injury to muscles or soft tissue. This is followed by abnormal bone formation with gradual restriction of movement and onset of deformity. Patients usually require a wheelchair by the time they reach their 20s.

Fibrodysplasia ossificans progressiva is a long-term debilitating and life-threatening disease because of loss of mobility and gradual impairment of breathing and heart function due to unwanted bone formation in the chest.

At the time of designation, fibrodysplasia ossificans progressiva affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 500 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).

No satisfactory methods of treatment were authorised in the EU for fibrodysplasia ossificans progressiva at the time of designation. Patients were mainly managed by avoidance of injuries that could trigger a flare-up, and treatment of the symptoms including anti-inflammatory medicines for the pain and inflammation.

In patients with fibrodysplasia ossificans progressiva, the ACVR1 receptor does not work as it should and this allows a substance called activin A to interact with the receptor and trigger bone formation. This medicine is a monoclonal antibody (a type of protein) that has been designed to attach to activin A, which stops activin A from interacting with ACVR1. This is expected to stop or reduce unwanted bone formation and reduce symptoms of the condition.

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 fibrodysplasia ossificans progressiva had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for fibrodysplasia ossificans progressiva 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.