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Orphan designation

On 17 January 2018, orphan designation (EU/3/17/1967) was granted by the European Commission to Millendo Therapeutics Ltd, United Kingdom, for N-[2,6-bis(1-methylethyl)phenyl]-N'-[[1-[4-(dimethylamino)phenyl]cyclopentyl]methyl]urea, hydrochloride salt (also known as ATR-101) for the treatment of congenital adrenal hyperplasia.

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia is a group of inherited conditions where patients are unable to produce normal amounts of the steroid hormones cortisol and aldosterone. These hormones play an important role in responding to stress and regulating salt and water in the body. The hormones are produced by the adrenal glands, two small glands that are located above the kidneys. In patients with the condition, the adrenal glands produce male sex hormones instead of cortisol and aldosterone. Congenital adrenal hyperplasia can be caused by many different mutations (changes) in the genes controlling the production of cortisol and aldosterone.

Congenital adrenal hyperplasia is long-term debilitating and life-threatening condition due to a failure of the response to stress (adrenal insufficiency), altered amounts of salt and water in the body, low blood pressure, and early puberty in boys or development of masculine characteristics in girls, which can lead to growth stopping early and short stature.

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

At the time of designation, congenital adrenal hyperplasia affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).

What treatments are available?

At time of designation, several products to treat congenital adrenal hyperplasia were authorised in the EU. In particular, various steroid hormones were used to replace those which are insufficiently produced by the adrenal gland and to control the production of excess male sex hormones.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with congenital adrenal hyperplasia because early data show that it reduces the levels of substances the body uses to produce male sex hormones. 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?

This medicine blocks an enzyme called ACAT1, which is involved in the production of male sex hormones. As an increase in male sex hormones is one of the effects of the disease, the medicine is expected to reduce some of the symptoms.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with congenital adrenal hyperplasia were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for congenital adrenal hyperplasia. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 December 2017 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>N-[2,6-bis(1-methylethyl)phenyl]-N'-[[1-[4-(dimethylamino)phenyl]cyclopentyl]methyl]urea, hydrochloride salt</p>
Active substanceN-[2,6-bis(1-methylethyl)phenyl]-N'-[[1-[4-(dimethylamino)phenyl]cyclopentyl]methyl]urea, hydrochloride salt
Medicine Name
Disease/conditionTreatment of congenital adrenal hyperplasia
Date of decision17/01/2018
Orphan decision numberEU/3/17/1967

Review of designation

Sponsor’s contact details

Millendo Therapeutics Ltd
Suite 1, 3rd Floor
11-12 St. James’s Square
London SW1Y 4LB
United Kingdom
Tel. +44 (0)20 7400 3395

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.