EU/3/16/1823: Orphan designation for the treatment of sudden sensorineural hearing loss

Sudden sensorineural hearing loss (SSNHL) is a sudden loss of hearing in one or sometimes both ears, caused by damage to the cells in the inner ear that detect sound and to the nerves that supply them. The damage can have various causes including loud noise, surgery and infection or it may occur as a side effect of certain medicines. Symptoms develop over a few days, and can include hearing loss, tinnitus (buzzing or ringing in the ears), a sensation of blockage and vertigo (dizziness). It is a long-term debilitating condition because of the often irreversible deafness it produces as well as tinnitus and vertigo.

At the time of designation, SSNHL affected approximately 4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 205,000 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 application, various medicines were authorised in the EU to treat symptoms associated with SSNHL such as tinnitus and vertigo. No medicines were authorised to treat the hearing loss itself.

The sponsor has provided sufficient information to show that pioglitazone hydrochloride might be of significant benefit for patients with SSNHL because laboratory studies suggest that it might help hearing to come back. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The way pioglitazone hydrochloride works in SSNHL is not fully understood. Pioglitazone hydrochloride activates a receptor called PPARγ in cells, and this is thought to reduce cell death, cell damage known as oxidative stress and inflammation, which are underlying causes of SSNHL. These effects are therefore expected to improve symptoms of SSHNL.

The effects of pioglitazone hydrochloride have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with pioglitazone hydrochloride in patients with SSNHL had been started.

At the time of submission, pioglitazone hydrochloride was authorised in the EU for type 2 diabetes.

At the time of submission, pioglitazone hydrochloride was not authorised anywhere in the EU for SSNHL 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.