EU/3/06/372: Orphan designation for the treatment of adrenal insufficiency

The adrenal gland consists of two small parts that are located above the kidneys, in the abdomen. The outer wall (cortex) of the adrenal gland secretes important steroid hormones. These include cortisol, aldosterone and dehydroepiandrosterone. Adrenal insufficiency is a rare disease that occurs when the adrenal glands do not produce enough of these hormones. Patients affected by this disease suffer of weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin. Adrenal insufficiency can also cause irritability and depression. Some patients experience reduced general health and impaired sexuality. Because the symptoms worsen slowly, they are usually ignored until a stressful event like an illness or an accident causes them to become worse. This can develop into acute adrenal insufficiency ('Addisonian crisis'), which is life-threatening.

At the time of designation, adrenal insufficiency affected less than 4.5 in 10,000 people in the European Union (EU). This is equivalent to a total of fewer than 211,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

Several products to treat adrenal insufficiency have been authorised, including hydrocortisone, oral tablets administered in two or three daily doses. In particular, various steroid hormones can be used to replace those that are insufficiently produced by the adrenal gland.

Hydrocortisone (modified-release tablet) might be of potential significant benefit for the treatment of adrenal insufficiency, because it is designed to mimic more closely the natural level of cortisol in the body, which has a variable profile over the day. In particular, it may improve the early morning fatigues and the patient's compliance to the treatment since it would be a single administration per day. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

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

At the time of submission of the application for orphan designation, no clinical trials in patients with adrenal insufficiency were initiated.

This specific formulation of hydrocortisone (modified-release tablet) was not authorised anywhere worldwide for adrenal insufficiency or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 April 2006 recommending the granting of this designation.

Update: Hydrocortisone (modified-release tablet) (Plenadren) was authorised in the EU on 3 November 2011 for treatment of adrenal insufficiency in adults.

• 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.