EU/3/14/1327

On 22 August 2014, orphan designation (EU/3/14/1327) was granted by the European Commission to Amyndas Pharmaceuticals S.A., Greece, for S3,S13-cyclo(D-tyrolsyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-aspartyl-L-tryptophyl-N-methyl-L-glycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-N-methyl-L-isoleucinamide) for the treatment of paroxysmal nocturnal haemoglobinuria.

What is paroxysmal nocturnal haemoglobinuria?

Paroxysmal nocturnal haemoglobinuria is a condition in which there is excessive breakdown of the patient’s red blood cells, leading to the release into the urine of a large amount of haemoglobin (the pigment contained in the cells). Because of the red colour of haemoglobin, the passing of red urine, particularly in the mornings, is usually the most obvious sign of the disease. Patients may also experience problems related to anaemia (low levels of red blood cells) such as tiredness and shortness of breath and problems related to blood clotting.

The condition is due to the lack of certain proteins on the surface of the red blood cells which normally protect them from being destroyed by the immune system (the body’s natural defences).

Paroxysmal nocturnal haemoglobinuria is a long-term debilitating and life-threatening condition due to its complications including abdominal pain, infection and kidney problems, and problems due to bleeding and blood clots.

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

At the time of designation, paroxysmal nocturnal haemoglobinuria affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, the medicine Soliris (eculizumab) was authorised in the EU for the treatment of paroxysmal nocturnal haemoglobinuria. Bone marrow transplantation to replace the defective cells was another therapy available to patients, however this treatment is available to only a small proportion of patients since a suitable donor is required. Other methods such as blood transfusions and treatment to prevent clotting with blood-thinning compounds can improve the symptoms in a small percentage of patients.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with paroxysmal nocturnal haemoglobinuria as it works differently to currently authorised treatment, and early studies in experimental models showed that it may be effective also in patients who do not respond to current treatment. 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 works by attaching to the C3 protein in the blood. This protein is part of a group of proteins known as the ‘complement system’, which normally helps the immune system to fight infections but which in patients with paroxysmal nocturnal haemoglobinuria also attacks red blood cells. By attaching to this protein, the medicine is expected to block or reduce the destruction of the red blood cells and thereby reduce 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 paroxysmal nocturnal haemoglobinuria had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for paroxysmal nocturnal haemoglobinuria 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 10 July 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.

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