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Orphan designation

On 27 October 2001, orphan designation (EU/3/11/919) was granted by the European Commission to Bioalliance Pharma SA, France, for clonidine hydrochloride for the prevention of oral mucositis in head and neck cancer patients undergoing radiation therapy.

In October 2014, BioAlliance Pharma changed name to Onxeo.

The sponsorship was transferred to Monopar Therapeutics Inc, in October 2017.

The sponsorship was transferred to Monopar Therapeutics SARL, in March 2018.

What is oral mucositis?

Oral mucositis is inflammation of the lining of the mouth which results in symptoms such as ulcers, severe pain, bleeding and inflammation. Patients with head and neck cancer are prone to developing oral mucositis because of the radiation therapy they receive. Radiation therapy employs high-dose X-rays or other high-energy rays to kill the cancer cells in the head and neck. Unfortunately the radiation therapy is also likely to cause inflammation in the surrounding cells and tissues.

Oral mucositis in head and neck cancer patients undergoing radiation therapy is a long-term debilitating and life threatening disease because it can lead to pain, poor nutrition, infections and make the patient less likely to comply with their radiotherapy treatment.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of oral mucositis was estimated to be approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 102,000 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).

*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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

What methods of prevention are available?

At the time of designation, mouth rinses containing calcium phosphate and povidone iodine were authorised in some EU countries for preventing oral mucositis in head and neck cancer patients undergoing radiation therapy.

The sponsor has provided sufficient information to show that clonidine hydrochloride might be of significant benefit for mucositis in head and neck cancer patients undergoing radiotherapy because it works in a different way to existing treatments and early studies show that it might offer benefits to patients with this condition, possibly in combination with existing methods. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Clonidine hydrochloride has been used for the treatment of high blood pressure since the 1970s. It is known to act on certain receptors in the body called ╬▒lpha-2 adrenergic receptors. Among other functions, these receptors are involved in the production of messenger molecules (cytokines) that are involved in inflammation. This includes cytokines that promote inflammation (pro-inflammatory) and others that reduce inflammation (anti-inflammatory). By attaching to these receptors, clonidine hydrochloride is expected to reduce the production of pro-inflammatory cytokines and increase the production of anti-inflammatory cytokines. This is expected to reduce inflammation which could help in preventing oral mucositis.

Clonidine hydrochloride is expected to be available as a tablet designed to adhere to the upper gum for several hours to allow the clonidine to dissolve slowly in the mouth.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, clinical trials with clonidine hydrochloride in patients with oral mucositis were ongoing.

At the time of submission, clonidine hydrochloride was not authorised anywhere in the EU for the prevention of oral mucositis 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 30 September 2011 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.

Key facts

Product details for <p>Clonidine hydrochloride</p>
Active substanceClonidine hydrochloride
Medicine Name
Disease/conditionPrevention of oral mucositis in head and neck cancer patients undergoing radiation therapy
Date of decision27/10/2011
Orphan decision numberEU/3/11/919

Review of designation

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

Sponsor’s contact details

Monopar Therapeutics SARL
12 rue Anselme
93400 Saint-Ouen

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.