EU/3/16/1816: Orphan designation for the treatment of oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy is a hereditary condition marked by weakness of the muscles around the eyes and throat, leading to symptoms such as drooping eyelids and difficulty swallowing. As muscle weakness progresses, weakness in other parts of the body may also develop, particularly in the arms near the shoulder and in the upper legs and hips. Patients usually present with this condition in their sixties or seventies.

The condition is caused by a mutation (change) in the gene that produces a protein called PABPN1. In patients with the mutation, an abnormal form of PABPN1 is produced, which builds up in muscle cells and stops muscles working properly.

Oculopharyngeal muscular dystrophy is debilitating in the long term because of its symptoms such as drooping eyelids and difficulty swallowing, and because it spreads to other parts of the body affecting mobility.

At the time of designation, oculopharyngeal muscular dystrophy affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 513,700,000 (Eurostat 2016).

At the time of submission of the application for orphan drug designation, there were no satisfactory treatments authorised for the condition. Patients were mainly treated with speech therapy, physiotherapy and surgery to help with drooping eyelids and swallowing difficulty.

This medicine consists of a virus that has been modified to contain genetic material that replaces the defective PABPN1 gene, together with other genetic material that stops the patient's defective gene from working. When given to patients, the virus is expected to carry the genetic material into muscle cells of the oesophagus (the tube that leads from the mouth to the stomach).

This would enable these muscle cells to produce the normal form of PABPN1 and stops production of abnormal PABPN1. Together, these effects are expected to improve muscle strength and thereby relieve symptoms affecting the oesophagus.

The virus used in this medicine (adeno-associated virus) does not cause disease in humans.

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

At the time of submission, no clinical trials with the medicine in patients with oculopharyngeal muscular dystrophy had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for oculopharyngeal muscular dystrophy 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 8 December 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.