EU/3/17/1873

On 22 May 2017, orphan designation (EU/3/17/1873) was granted by the European Commission to Best Regulatory Consulting Ltd, United Kingdom, for poly(oxy-1,2-ethanediyl),.alpha.-hydro-.omega.-hydroxy-,15,15'-diester with N-acetyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-.alpha.-aspartyl-L-tryptophylglycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-L-threonyl-2-[2-(2-aminoethoxy)ethoxy]acetyl-N6-carboxy-L-lysinamide cyclic (2.fwdarw.12)-(disulfide); where two identical synthetic peptide domains are covalently linked at the ends of the polyethylene glycol chain (also known as APL-2) for the treatment of paroxysmal nocturnal haemoglobinuria.

What is paroxysmal nocturnal haemoglobinuria?

Paroxysmal nocturnal haemoglobinuria (PNH) is a condition in which there is excessive breakdown of red blood cells (haemolysis), leading to the release into the urine of a large amount of haemoglobin (the protein found in red blood cells that carries oxygen around the body). 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 blood clotting.

The condition is caused by 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).

PNH 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, PNH affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 515,700,000 (Eurostat 2017).

What treatments are available?

At the time of designation, the medicine Soliris (eculizumab) was authorised in the EU for the treatment of PNH. Bone marrow transplantation to replace the defective red blood cells was another therapy available to patients. Other methods such as blood transfusions and treatment with blood-thinning compounds to prevent clotting were used in some patients to improve symptoms.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with PNH because preliminary data show that the medicine improved haemoglobin levels in patients in whom haemolysis was not controlled by currently authorised treatments. 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 part of the immune system involved in damaging the red blood cells of patients with PNH is called the ‘complement system’.

This medicine is made of two synthetic peptides (short chains of amino acids) linked together, which target and attach to an important protein in the complement system called C3. By attaching to C3, the medicine is expected to block the chain of reactions that damage the red blood cells, thus relieving the symptoms of the disease.

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 PNH were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for PHN. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 April 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.

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