EU/3/06/372

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Orphan designation

On 22 May 2006, orphan designation (EU/3/06/372) was granted by the European Commission to DuoCort AB, Sweden, for hydrocortisone (modified-release tablet) for the treatment of adrenal insufficiency.

The sponsorship was transferred to DuoCort Pharma AB, Sweden, in November 2008 and subsequently to ViroPharma SPRL, Belgium, in February 2012.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is 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.

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

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).

What treatments are available?

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.

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 the natural cortisol that is missing due to the adrenal insufficiency, 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 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.

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 NamePlenadren
Disease/conditionTreatment of adrenal insufficiency
Date of decision22/05/2006
OutcomePositive
Orphan decision numberEU/3/06/372

Review of designation

During its meeting of 6-8 September 2011, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/06/372 for Plenadren (hydrocortisone) as an orphan medicinal product for the treatment of adrenal insufficiency. 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 satisfactory methods of treatment. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained.

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

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Plenadren for ‘treatment of adrenal insufficiency in adults’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2006. Adrenal insufficiency remains a condition that is debilitating in the long term because of tiredness and weakness that affect quality of life. If left untreated the condition can be life-threatening, as it can progress rapidly to adrenal crisis leading to shock and death.

Prevalence of the condition

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of adrenal insufficiency 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 less than 4.5 people in 10,000. This is equivalent to a total of fewer than 228,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of adrenal insufficiency, including hydrocortisone oral tablets administered in two or three daily doses, and synthetic glucocorticoids (steroid hormones).

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Plenadren in adrenal insufficiency is justified on the basis that the once-daily modified-release formulation produces levels of active substance in the body which more closely mimic the natural release pattern of the hormone in healthy people compared with existing treatments. This offers a major contribution to patient care.

Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Plenadren is of significant benefit for adult patients affected by adrenal insufficiency.

Conclusion

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Plenadren still meets the criteria for designation as an orphan medicinal product and that Plenadren should remain in the Community register of orphan medicinal products.

Related information

Sponsor’s contact details:

ViroPharma SPRL
Rue Montoyer 47
1000 Brussels
Belgium
Tel. +32 2 747 09 71
Fax +32 2 747 09 42
E-mail: john.watson@viropharma.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.