EU/3/07/459

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Orphan designation

On 10 July 2007, orphan designation (EU/3/07/459) was granted by the European Commission to Bioprojet, France, for 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride for the treatment of narcolepsy.

In November 2015, Bioprojet changed name to Bioprojet Pharma.

Update: 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride (Wakix) has been authorised in the EU since 31 March 2016. Wakix is indicated in adults for the treatment of narcolepsy with or without cataplexy.

More information on Wakix can be found in the European public assessment report (EPAR).

What is Narcolepsy?

Narcolepsy is characterised by excessive daytime sleepiness (patients have an irresistible urge to sleep, even in inappropriate times and places), and often have disturbed night sleep with very vivid dreams. In addition, some of the patients experience sudden episodes of severe muscle weakness (called cataplexy), potentially causing dangerous falls. Narcolepsy symptoms can be very severe and damage significantly both the private and professional life of the patients. Cataplexy can increase the risk of accidents, including car accidents. It can occur so suddenly that the patient does not have time to prepare and avoid falls or sudden attacks of sleep urge, for example.

What are the methods of treatment available?

Several products to treat the symptoms of narcolepsy were authorised in the Community at the time of submission of the application for orphan drug designation. 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine may be of potential significant benefit in patients affected by narcolepsy. This will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

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

According to the information provided by the sponsor, narcolepsy was considered to affect not more than 230,000 persons* in the European Union.


* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

The mechanism of action of 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine in narcolepsy is not fully understood. It may involve regulation of neurotrasnmitters, which are chemical substances produced in the brain and used by brain cells to communicate between themselves, and this may improve the night sleep and indirectly decrease also the daytime symptoms.

What is the stage of development of this medicinal product?

The effects of 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine were evaluated in experimental models. 

At the time of submission of the application for orphan designation, clinical trials in patients with narcolepsy were ongoing.

1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine was not authorised anywhere worldwide for narcolepsy or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 31 May 2007 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition,
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride</p>
Active substance1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride
Medicine Name
Disease/conditionTreatment of narcolepsy
Date of decision10/07/2007
OutcomePositive
Orphan decision numberEU/3/07/459

Review of designation

During its meeting of 16 to 18 February 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/07/459 for Wakix (pitolisant1) as an orphan medicinal product for the treatment of narcolepsy. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with narcolepsy. The COMP recommended that the orphan designation of the medicine be maintained2.


1Previously known as 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride.

2The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Wakix for the treatment of narcolepsy with or without cataplexy in adults.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of narcolepsy’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2007. Narcolepsy remains a condition that is long-term debilitating because it causes excessive daytime sleepiness and cataplexy (sudden muscle weakness), increasing the risk of accidents and interfering with normal life.

Prevalence of the condition

The sponsor provided updated information on the prevalence of narcolepsy based on data from the published literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of narcolepsy remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 4 people in 10,000. This is equivalent to a total of around 205,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, modafinil and sodium oxybate were authorised in the EU for the treatment of narcolepsy.

Significant benefit of Wakix

The COMP concluded that the claim of a significant benefit of Wakix over modafinil is justified because Wakix can be tolerated better by patients and has been shown to have a positive effect on cataplexy.

When compared with sodium oxybate, Wakix was considered to improve patient care because it is to be taken by mouth once a day, whereas sodium oxybate has a more complex dosing schedule which includes dose titration (increasing the dose slowly) over several weeks. In addition, sodium oxybate is given twice at night, which may disrupt sleep.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Wakix is of significant benefit to patients affected by narcolepsy.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Wakix still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Further information on the current regulatory status of Wakix can be found in the European public assessment report (EPAR).

Related information

Sponsor’s contact details

Bioprojet Pharma
9 rue Rameau
75002 Paris
France
Tel. + 33 1 4703 6633
Fax + 33 1 4703 6630
E-mail: contact@bioprojet.com

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.