EU/3/05/296

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Orphan designation

On 27 July 2005, orphan designation (EU/3/05/296) was granted by the European Commission to Professor Richard JM Ross, United Kingdom, for hydrocortisone (modified release tablet) for the treatment of congenital adrenal hyperplasia.
The sponsorship was transferred to Phoqus Pharmaceuticals Limited, United Kingdom, in December 2006 and subsequently to Diurnal Limited, United Kingdom, in February 2009.

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia is an inherited condition that is present from birth and causes a diffuse enlargement of the adrenal glands. The adrenal gland consists of two small glands that are located above the kidneys, in the abdomen. The outer wall (cortex) of the adrenal gland secretes important substances, so-called steroid hormones. Steroid hormones include sex hormon’es and hormones used to control minerals and sugar in the body. These include cortisol, aldosterone and dehydroepiandrosterone. The formation and activation of these hormones depends on certain specific proteins (enzymes). The lack or malfunctioning of one of these enzymes, due to a genetic defect, will result in the blocking of the production of cortisol and aldosterone from the adrenal gland. This will then lead to an overproduction of male sex hormones.
Congenital adrenal hyperplasia is chronically debilitating. The metabolism of salt and water is disturbed causing dehydration, low blood pressure and loss of weight. The affected individuals may also develop excessive pigmentation in the skin. In boys, the syndrome produces early development of masculine characteristics and, in girls, it may lead to enlargement of the genital tract, lack of menstruation, deep voice and excessive hair (this phenomenon is called “virilisation”). In both sexes, the syndrome may result in short stature.

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

At the time of designation, congenital adrenal hyperplasia affected not more than 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more than 46,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

What treatments are available?

Several products to treat congenital adrenal hyperplasia have been authorised. In particular, various steroid hormones can be used to replace those which are insufficiently produced by the adrenal gland. Hydrocortisone (modified release tablet) might be of potential significant benefit for the treatment of congenital adrenal hyperplasia because it is designed to mimic more closely the level of cortisol in the body. It may improve patient’s acceptance of the treatment and prevent problems of masculinisation (or virilisation), infertility and excess steroid treatment. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Hydrocortisone (also known as cortisol) is the main steroid hormone secreted by the adrenal gland. Hydrocortisone (modified release tablet) is expected to replace natural the cortisol that is missing due to the congenital adrenal hyperplasia, and this may help to treat the symptoms of the disease.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, no clinical trials in patients with congenital adrenal hyperplasia were initiated.
This specific formulation of hydrocortisone (modified release tablet) was not authorised anywhere worldwide for congenital adrenal hyperplasia 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 15 June 2005 a positive opinion recommending the grant of the above-mentioned 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 Community) 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>Hydrocortisone (modified release tablet)</p>
Active substanceHydrocortisone (modified release tablet)
Medicine Name
Disease/conditionTreatment of congenital adrenal hyperplasia
Date of decision27/07/2005
OutcomePositive
Orphan decision numberEU/3/05/296

Review of designation

Sponsor’s contact details:

Diurnal Limited
University of Sheffield
Room 112 Floor M
Royal Hallamshire Hospital
Glossop Road
Sheffield S10 2JF
United Kingdom
Telephone: + 44 114 271 3305
Telefax: + 44 114 271 1863

Patients’ associations contact points:

Association Surrenales 
Addison's disease, Cushings' CAH and other related disorders 
3 boulevard de la Rochette
42700 Firminy
France 
E-mail: carolinebellevoix@hotmail.com

Congenital Adrenal Hyperplasia Support Group (CAHG) 
CAH and related adrenal disorders 
Contact: Mrs. Sue Elford
2 Windrush Close
Flitwick Bedfordshire
MK45 1PX 
United Kingdom 
Telephone: +44 15 25 71 75 36

Climb CAH UK SUPPORT GROUP
Climb Building 176 Nantwich Road
Crewe
CW2 6BG
United Kingdom
Telephone: +44 87 07 70 03 26
E-mail: webmaster@cah.org.uk