EU/3/18/2108 - orphan designation for treatment of congenital adrenal hyperplasia

adeno-associated viral vector expressing human 21- hydroxylase

Overview

On 14 December 2018, orphan designation (EU/3/18/2108) was granted by the European Commission to Pharma Gateway AB, Sweden, for adeno-associated viral vector expressing human 21-hydroxylase for the treatment of congenital adrenal hyperplasia.

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia is a group of inherited conditions where patients’ adrenal glands (two small glands located above each kidney) are unable to produce normal amounts of the steroid hormones cortisol and aldosterone. These hormones are important for dealing with stress on the body and regulating salt and water in the body. In patients with the condition, these glands may produce increased amounts of male sex hormones. 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 a long-term debilitating and life-threatening condition because it can reduce the ability of the body to deal with physical stress, change the amounts of salt and water in the body, and reduce blood pressure. The condition can also cause early puberty in boys and development of masculine characteristics in girls, which can lead to growth stopping early and reduced height.

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

At the time of designation, congenital adrenal hyperplasia affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 52,000 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).

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*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 517,400,000 (Eurostat 2018).

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 laboratory data suggest that it improves production of steroid hormones without the need for corticosteroids.

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?

Most patients with congenital adrenal hyperplasia have mutations in the gene responsible to produce the enzyme 21-hydroxylase, which is one of the enzymes involved in the production of cortisol and aldosterone. Because of these mutations, patients lack 21-hydroxylase and are therefore unable to produce normal amounts of these hormones.

This medicine is made of a virus containing a normal copy of the gene for 21-hydroxylase. The virus is expected to deliver the gene into adrenal gland cells and enable them to produce the enzyme. This is expected to help relieve symptoms of the disease.

The type of virus used in this medicine (‘adeno-associated virus’) does not cause disease in humans.

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, no clinical trials with the medicine in patients with congenital adrenal hyperplasia had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for congenital adrenal hyperplasia 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 8 November 2018 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.

EU/3/18/2108: Public summary of opinion on orphan designation: Adeno-associated viral vector expressing human 21-hydroxylase

Adopted Reference Number: EMA/818775/2018

Key facts

• Active substance:
  adeno-associated viral vector expressing human 21- hydroxylase
• Intended use:
  Treatment of congenital adrenal hyperplasia
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2108
• Date of designation:
  14/12/2018
• Sponsor:

  Pharma Gateway AB;

Review of designation

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