EU/3/19/2206 - orphan designation for treatment of Alexander disease

2'-O-(2-methoxyethyl)-D-ribose antisense oligonucleotide targeting glial fibrillary acidic protein messenger ribonucleic acid

Overview

On 17 October 2019, orphan designation EU/3/19/2206 was granted by the European Commission to Ionis Development (Ireland) Limited, Ireland, for 2'-O-(2-methoxyethyl)-d-ribose antisense oligonucleotide targeting glial fibrillary acidic protein messenger ribonucleic acid (also known as ION-1166998) for the treatment of Alexander disease.

What is Alexander disease?

Alexander disease is a genetic disorder of brain cells called astrocytes in the so-called white matter of the brain. It is caused by a mutation (change) in a gene that makes the protein GFAP (glial fibrillary acidic protein), which is needed for the growth and function of these cells. The change results in too much of the protein being made, interfering with normal function.

The disorder usually begins in infancy and causes the gradual loss of bodily and mental functions; symptoms can include seizures, spasticity, developmental disorders, enlargement of the head, and problems with speech and movement (including abnormal eye and facial movement and difficulty swallowing). Another form begins later in life and causes difficulty swallowing and speaking, and problems with coordination and movement.

Alexander disease is a severe, progressive and debilitating condition that can eventually result in death due to loss of control over automatic functions like breathing. Infants and young children who develop the condition rarely survive beyond the teenage years or young adulthood.

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

At the time of designation, Alexander disease affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of Alexander disease. Patients received supportive treatment to manage the symptoms of the condition, including medicines to manage seizures.

How is this medicine expected to work?

The medicine is an 'antisense oligonucleotide', a small strand of synthetic genetic material. It has been designed to stop the altered gene from working and producing so much GFAP protein. By reducing the excessive production of GFAP in patients with Alexander disease, the medicine is expected to help control the condition.

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 Alexander disease had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for the treatment of Alexander disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 12 September 2019, 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/3/19/2206: Public summary of positive opinion for orphan designation of 2'-O-(2-Methoxyethyl)-d-ribose antisense oligonucleotide targeting glial fibrillary acidic protein messenger ribonucleic acid for the treatment of Alexander disease

AdoptedReference Number: EMADOC-628903358-1522

Key facts

• Active substance:
  2'-O-(2-methoxyethyl)-D-ribose antisense oligonucleotide targeting glial fibrillary acidic protein messenger ribonucleic acid
• Intended use:
  Treatment of Alexander disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2206
• Date of designation:
  17/10/2019
• Sponsor:

  Ionis Development (Ireland) Limited