EU/3/20/2250 - orphan designation for treatment of Duchenne muscular dystrophy

Adeno-associated virus serotype rh74 containing the human micro-dystrophin gene

Overview

On 28 February 2020, orphan designation EU/3/20/2250 was granted by the European Commission to Sarepta Therapeutics Ireland Limited, Ireland, for adeno-associated virus serotype rh74 containing the human micro-dystrophin gene (also known as SRP-9001) for the treatment of Duchenne muscular dystrophy.

The sponsorship was transferred to Roche Registration GmbH, Germany, in October 2020.

What is Duchenne muscular dystrophy?

Duchenne muscular dystrophy is a genetic disease that causes increasing weakness and atrophy (wasting) of muscles. It mainly affects boys, and usually starts before the age of 6 years. The muscle weakness usually starts in the hips and legs, before affecting the arms, chest and the heart. Patients with DMD lack normal dystrophin, a protein found in muscles. Because this protein helps to protect muscles from injury as muscles contract and relax, in patients with the disease the muscles become progressively weaker and eventually stop working.

Duchenne muscular dystrophy causes long-term disability and is life threatening because of its effects on the heart and the respiratory muscles (muscles that are used to breathe). The disease usually leads to death in early adulthood.

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

At the time of designation, Duchenne muscular dystrophy affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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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^*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, Norway, Iceland and Liechtenstein. This represents a population of 519,200,000 (Eurostat 2020).

What treatments are available?

At the time of designation, the medicine Translarna (ataluren) was authorised in the EU for the treatment of a small group of patients with Duchenne muscular dystrophy caused by a particular type of mutation (change), called a nonsense mutation, in the dystrophin gene. Patients also received supportive treatment such as physiotherapy.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with Duchenne muscular dystrophy because early studies showed that the condition improved in children treated with the medicine. Also, it has the potential to work in patients with all forms of the dystrophin gene mutation. By contrast, Translarna is for use in patients with only one form of mutation.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?

The medicine is made of a virus that contains genetic material for producing a shortened, but working, form of dystrophin. The medicine is designed to introduce the genetic material into muscles and the heart. A single injection is expected to enable the patient to produce a working form of dystrophin and so slow down progression of the disease.

The type of 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, clinical trials with the medicine in patients with Duchenne muscular dystrophy were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Duchenne muscular dystrophy. Orphan designation of the medicine had been granted in the United States for Duchenne muscular dystrophy.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 22 January 2020, 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/3/20/2250: Public summary of positive opinion for orphan designation of adeno-associated virus serotype rh74 containing the human micro-dystrophin gene for the treatment of Duchenne muscular dystrophy

Reference Number: EMADOC-628903358-1934

Key facts

• Active substance:
  Adeno-associated virus serotype rh74 containing the human micro-dystrophin gene
• Intended use:
  Treatment of Duchenne muscular dystrophy
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/20/2250
• Date of designation:
  28/02/2020
• Sponsor:

  Roche Registration GmbH; Emil-Barell-Strasse 1; Grenzach; 79639 Grenzach-Wyhlen; Germany; Tel. [phone]; E-mail: [e-mail]