EU/3/15/1556

On 9 October 2015, orphan designation (EU/3/15/1556) was granted by the European Commission to TMC Pharma Services Ltd, United Kingdom, for recombinant adeno-associated viral vector expressing the human CNGA3 gene for the treatment of achromatopsia caused by mutations in the CNGA3 gene.

What is achromatopsia caused by mutations in the CNGA3 gene?

Achromatopsia is an inherited disease of the eye that leads to reduced visual acuity (how well a person can see), colour blindness, severe photophobia (increased sensitivity to light) and nystagmus (fast involuntary eye movements). Achromatopsia is a disorder of the retina (the light-sensitive surface at the back of the eye). In patients with achromatopsia, a type of retina cells called ‘cone photoreceptors’, which provide vision in bright light including colour vision, do not function normally.

In around a quarter of achromatopsia patients, the disease is caused by mutations (changes) in the CNGA3 gene. Achromatopsia is a long-term debilitating disease because it affects how well a person can see in bright light, which may limit everyday activities.

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

At the time of designation, achromatopsia caused by mutations in the CNGA3 gene affected less than 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 15,000 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, no satisfactory methods were authorised in the EU for treating achromatopsia caused by mutations in the CNGA3 gene. Patients with the condition were given glasses with red-coloured lenses to reduce light sensitivity, as well as low vision aids such as magnifiers for reading.

How is this medicine expected to work?

In this disease, a protein involved in the normal functioning of cone photoreceptors, called ‘CNGA3 protein’, does not work properly due to defects in the gene responsible for producing it.

This medicine is made up of a virus that contains a normal copy of the CNGA3 gene. When injected into the patient’s eyes, it is expected that the virus will carry the CNGA3 gene into photoreceptor cells, so that a functional CNGA3 protein can be produced. This is expected to enable cone photoreceptors to work properly, thereby preventing the symptoms 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?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with achromatopsia caused by mutations in the CNGA3 gene had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for achromatopsia caused by mutations in the CNGA3 gene 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 3 September 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.

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