EU/3/15/1481 - orphan designation for treatment of Huntington’s disease

Phenol, 4-[2-(aminomethyl)-4-thiazolyl]-2,6-bis(1,1-dimethylethyl) monohydrochloride

Overview

Please note that this product was withdrawn from the Community register of designated orphan medicinal products in September 2017 on request of the sponsor.

On 24 April 2015, orphan designation (EU/3/15/1481) was granted by the European Commission to Ipsen Pharma, France, for phenol, 4-[2-(aminomethyl)-4-thiazolyl]-2,6-bis(1,1-dimethylethyl) monohydrochloride for the treatment of Huntington's disease.

What is Huntington's disease?

Huntington's disease is a hereditary disease that causes brain cells to die. This leads to symptoms such as involuntary jerky movements, behavioural problems and dementia (loss of intellectual function). The disease is usually first noticed between 35 and 45 years of age, and gets worse over time.

Huntington's disease is caused by defects in the gene responsible for the production of a protein called huntingtin. The gene abnormalities result in an abnormal form of the protein being produced, which causes damage to the cells in specific areas of the brain.

Huntington's disease is a debilitating and life-threatening condition because it causes severe behavioural and mental problems, a progressive loss of the ability to move and potentially life-threatening complications.

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

At the time of designation, Huntington's disease affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, the treatments authorised in the EU for Huntington's disease were aimed at relieving the symptoms of the disease. In some Member States, haloperidol, pimozide, tetrabenazine and tiapride were authorised for the abnormal involuntary movements that occur in Huntington's disease. In addition, benzodiazepines were used for anxiety, and antidepressants and lithium to treat depression and mood swings.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with Huntington's disease because early studies in experimental models indicate that the medicine may reduce brain damage, and improve movement as well as survival. 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?

In Huntington's disease, the abnormal huntingtin protein interferes with several cell processes that ultimately lead to the death of nerve cells, such as the transmission of signals and the normal functioning of mitochondria (structures located inside cells, which produce the energy necessary for cells to function).

This medicine is expected to work in Huntington's disease in different ways: by neutralising oxygen free radicals, which are toxic substances that accumulate in mitochondria when they are not functioning normally; by reducing inflammation by blocking enzymes known as cyclooxygenases; and by reducing overstimulation of brain cells by the neurotransmitter (nerve signalling molecule) glutamate, which can lead to injury and cell death. These actions are expected to protect brain cells from degenerating in patients with Huntington's disease.

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, clinical trials with the medicine in patients with Huntington's disease were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for Huntington's disease 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 19 March 2015 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/3/15/1481: Public summary of positive opinion for orphan designation of Phenol, 4-[2-(aminomethyl)-4-thiazolyl]-2,6-bis(1,1-dimethylethyl) monohydrochloride for the treatment of Huntington’s disease

AdoptedReference Number: EMA/COMP/205588/2015

Key facts

• Active substance:
  Phenol, 4-[2-(aminomethyl)-4-thiazolyl]-2,6-bis(1,1-dimethylethyl) monohydrochloride
• Intended use:
  Treatment of Huntington’s disease
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/15/1481
• Date of designation:
  24/04/2015
• Sponsor:

  Ipsen Pharma;

Review of designation

Please note that this product was withdrawn from the Community register of designated orphan medicinal products in September 2017 on request of the sponsor.