EU/3/16/1771 - orphan designation for treatment of glycogen storage disease type Ia

adeno-associated viral vector serotype 8 containing the human glucose-6-phosphatase gene (pariglasgene brecaparvovec)

Overview

This medicine is now known as pariglasgene brecaparvovec.

On 18 November 2016, orphan designation (EU/3/16/1771) was granted by the European Commission to Pharma Gateway AB, Sweden, for adeno-associated viral vector serotype 8 containing the human glucose-6-phosphatase gene (also known as DTX401) for treatment of glycogen storage disease type Ia.

The sponsorship was transferred to Ultragenyx Germany GmbH, Germany, in September 2020.

The sponsor’s address was updated in November 2020.

What is glycogen storage disease type Ia?

Glycogen storage disease type Ia is an inherited disorder where there is build-up of glycogen (a complex sugar stored in the body) mainly in the liver, kidneys and gut. The disease is caused by the lack of an enzyme called glucose 6-phosphatase which is involved in the breakdown of glycogen into glucose (a simpler sugar). Patients have a wide range of signs and symptoms, including enlarged liver and kidneys, poor growth, frequent bacterial infections and ulcers in the mouth and gut.

Glycogen storage disease type Ia is a long-term debilitating and life-threatening disease because it causes liver and kidney problems, anaemia (low red blood cell counts), osteoporosis (fragile bones) and can lead to development of liver cancer.

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

At the time of designation, glycogen storage disease type Ia affected approximately 0.08 in 10,000 people in the European Union (EU). This was equivalent to a total of around 4,000 people¹, 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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¹Disclaimer: 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, there was no satisfactory method authorised for the treatment of glycogen storage disease type Ia in the EU. Patients with the disease were placed on a strict diet to maintain normal glucose levels. Calcium and vitamin D supplements were given to prevent bone fractures and iron supplements were given to avoid anemia.

How is this medicine expected to work?

This medicine consists of a virus that has been modified to contain a gene that produces normal glucose 6-phosphatase. When given to patients, the virus is expected to carry this gene into liver cells. This would enable these cells to produce glucose 6-phosphatase so that glycogen can be broken down to glucose. This is expected to reduce symptoms of the condition.

The 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 glycogen storage disease Ia had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for glycogen storage disease Ia 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 6 October 2016 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/3/16/1771: Public summary of positive opinion for orphan designation of adeno-associated viral vector serotype 8 containing the human glucose-6-phosphatase gene for treatment of glycogen storage disease type Ia

Key facts

• Active substance:
  adeno-associated viral vector serotype 8 containing the human glucose-6-phosphatase gene (pariglasgene brecaparvovec)
• Intended use:
  treatment of glycogen storage disease type Ia
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1771
• Date of designation:
  18/11/2016
• Sponsor:

  Ultragenyx Germany GmbH;