EU/3/14/1404 - orphan designation for treatment of multiple system atrophy

1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one (verdiperstat)

Overview

This medicine is now known as verdiperstat.

On 16 December 2014, orphan designation (EU/3/14/1404) was granted by the European Commission to Astra Zeneca AB, Sweden, for 1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one for the treatment of multiple system atrophy.

The sponsorship was transferred to Richardson Associates Regulatory Affairs Limited, Ireland, in March 2019.

The sponsorship was transferred to Biohaven Pharmaceutical Ireland DAC, Ireland, in September 2021.

What is multiple system atrophy?

Multiple system atrophy is a progressive disease of the nervous system, where nerve cells in the certain areas of the brain and spinal cord gradually deteriorate, causing loss of voluntary and involuntary muscle function. This leads to symptoms such as impotence in men and loss of bladder control as well as shaking, rigidity and/or loss of muscle coordination, light-headedness due to orthostatic hypotension (excessive drop in blood pressure) and difficulties with speech, breathing and gait (the way a person walks). Some of these features are similar to those seen in Parkinson's disease, which makes these disorders difficult to be distinguished in the early stages of the disease.

Multiple system atrophy is a long-term debilitating and life-threatening disease because of the gradual loss of muscle function and its effects on muscles used for breathing.

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

At the time of designation, multiple system atrophy affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, there were no satisfactory methods authorised in the EU for the treatment of multiple system atrophy. Different treatments were used to relieve the symptoms of the disease, such as beta blockers and vasopressin for the treatment of hypotension (low blood pressure) and anticholinergic medicines to treat bladder problems. Parkinson medicines such as levodopa are not effective in treating the Parkinson-type symptoms of multiple system atrophy.

How is this medicine expected to work?

The cause of the damage to nerves cells in multiple system atrophy is unclear but there is evidence that toxic molecules containing oxygen called 'reactive nitrogen species' (NOS) could be involved.

This medicine is expected to work by blocking the action of an enzyme called myeloperoxidase, which generates NOS in the nervous system. By reducing NOS the medicine is expected to improve the symptoms of multiple system atrophy.

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 multiple system atrophy were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for multiple system atrophy 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 13 November 2014 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/3/14/1404: Public summary of opinion on orphan designation: 1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one for the treatment of multiple system atrophy

Adopted Reference Number: EMA/COMP/722694/2014

Key facts

• Active substance:
  1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d] pyrimidin-4-one (verdiperstat)
• Intended use:
  Treatment of multiple system atrophy
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/14/1404
• Date of designation:
  16/12/2014
• Sponsor:

  Biohaven Bioscience Ireland Limited

Review of designation

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