EU/3/14/1368

On 19 November 2014, orphan designation (EU/3/14/1368) was granted by the European Commission to Medpace Germany GmbH, Germany, for palovarotene for the treatment of fibrodysplasia ossificans progressiva.

What is fibrodysplasia ossificans progressiva?

Fibrodysplasia ossificans progressiva is a genetic condition which causes abnormal formation of bone in the muscles, tendons, ligaments and other tissues. It is caused by a mutation (defect) in the gene for a receptor in cells that form bone and cartilage. This receptor is normally switched on by a protein called bone morphogenetic protein, triggering processes that lead to formation of bone. However, in patients with the mutation it is permanently switched on, leading to the formation of extra, unwanted bone in muscles and joints throughout the body.

Patients experience episodes of pain, inflammation and swelling (‘flare-ups’), often triggered by minor injury to muscles or soft tissues, followed by abnormal bone formation with gradual restriction of movement and deformity. Patients usually require a wheelchair by the time they reach their third decade of life.

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 bone formation in the chest.

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

At the time of designation, fibrodysplasia ossificans progressiva affected approximately 0.006 in 10,000 people in the European Union (EU). This was equivalent to a total of around 300 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 511,100,000 (Eurostat 2014).

What treatments are available?

No satisfactory methods of treatment were authorised in the EU for fibrodysplasia ossificans progressiva at the time of application. 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.

How is this medicine expected to work?

Palovarotene belongs to a class of medicines known as retinoids. It attaches to another receptor in cells, called the retinoic acid receptor gamma, switching on processes that reduce bone formation. Palovarotene is therefore expected to help prevent the abnormal bone formation seen in fibrodysplasia ossificans progressiva and relieve the symptoms of the condition.

What is the stage of development of this medicine?

The effects of palovarotene have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with palovarotene in patients with fibrodysplasia ossificans progressiva was ongoing.

At the time of submission, palovarotene was not authorised anywhere in the EU for fibrodysplasia ossificans progressiva. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 2014 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 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.