EU/3/17/1870 - orphan designation for treatment of mitochondrial DNA depletion syndrome, myopathic form

thymidine

deoxycytidine

Overview

On 20 April 2017, orphan designation (EU/3/17/1870) was granted by the European Commission to Vall d'Hebron Institute of Research, Spain, for thymidine and deoxycytidine for treatment of mitochondrial DNA depletion syndrome, myopathic form.

What is mitochondrial DNA depletion syndrome, myopathic form?

Mitochondrial DNA depletion syndrome is a group of genetic diseases in which patients' cells have reduced amounts of mitochondrial DNA. Mitochondria are parts of the cell that produce the cell's energy and they carry their own genetic material, mitochondrial DNA. The 'myopathic form' of the disease affects mainly the muscles and causes muscle weakness, including in the limbs and in muscles required for breathing and feeding. Symptoms usually begin to appear in early childhood. The condition is debilitating and life-threatening because of its widespread effects on muscles leading to loss of movement and inability to breathe.

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

At the time of designation, the myopathic form of mitochondrial DNA depletion syndrome affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 515,700,000 (Eurostat 2017).

What treatments are available?

At the time of the orphan designation no satisfactory methods were authorised in the EU for the treatment of the myopathic form of mitochondrial DNA depletion syndrome. Treatment was mainly supportive with patients being fed via a feeding tube and getting help with breathing through physiotherapy and ventilator machines.

How is this medicine expected to work?

In patients with the myopathic form of mitochondrial DNA depletion syndrome, the enzyme thymidine kinase 2 (TK2), which is used to produce and maintain mitochondrial DNA, does not work well.

This medicine contains two substances – thymidine and deoxycytidine – also used to make mitochondrial DNA. By increasing the levels of thymidine and deoxycytidine in the body, the medicine is expected to make up for the deficiencies in TK2 activity, thereby improving the production of mitochondrial DNA and helping relieve the patient's symptoms.

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 the myopathic form of mitochondrial DNA depletion syndrome had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the condition. Orphan designation of the medicine has been granted in the United States for treatment of thymidine kinase 2 deficiency.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 March 2017 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/3/17/1870: Public summary of opinion on orphan designation: Thymidine and deoxycytidine for treatment of mitochondrial DNA depletion syndrome, myopathic form

Adopted Reference Number: EMA/210409/2017

Key facts

• Active substance:
  • thymidine
  • deoxycytidine
• Intended use:
  Treatment of mitochondrial DNA depletion syndrome, myopathic form
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1870
• Date of designation:
  20/04/2017
• Sponsor:

  UCB Pharma;

Review of designation

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