EU/3/15/1547: Orphan designation for the treatment of narcolepsy

Narcolepsy is a sleep disorder which affects the brain's ability to regulate the sleep-wake cycle. This can lead to symptoms such as irresistible urge to sleep, even at inappropriate times and places, and disturbed night-time sleep. Some patients have episodes of severe muscle weakness (cataplexy) that can cause collapse.

Narcolepsy is a long-term debilitating disease because it causes excessive daytime sleepiness and cataplexy, increasing the risk of accidents and interfering with normal life. The condition can be life-threatening.

At the time of designation, narcolepsy affected less than 4 in 10,000 people in the European Union (EU). This was equivalent to fewer than 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 512,900,000 (Eurostat 2015).

At the time of designation, several medicines were authorised in the EU for narcolepsy. They included modafinil and sodium oxybate. Some medicines such as methylphenidate, caffeine, clomipramine and imipramine were used off-label to treat this condition.

The sponsor has provided sufficient information to show that mazindol might be of significant benefit for patients with narcolepsy because early clinical studies showed beneficial effects in patients who did not respond to current treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Mazindol is an anorectic (appetite suppressant) medicine that was developed for the treatment of obesity in the 1960's. It was withdrawn, as were all anorectics, from the market in the EU at the end of the 90's but remained authorised outside the EU.

Although the way mazindol works in narcolepsy is not clearly understood, it is expected to work in a similar way to amphetamines by increasing the levels of dopamine and noradrenaline in the brain. Dopamine and noradrenaline are neurotransmitters (chemical messengers) that carry signals between brain cells, including those that promote alertness and wakefulness.

As mazindol is a well-known substance, the sponsor provided data from the published literature to support its application for orphan designation.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with narcolepsy had been started by the sponsor.

At the time of submission, mazindol was not authorised anywhere in the EU for narcolepsy. Orphan designation of mazindol had previously been granted in the EU for narcolepsy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 September 2015 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.