EU/3/03/166: Orphan designation for the treatment of paroxysmal nocturnal haemoglobinuria

PNH is a disorder in which red blood cells lack specific proteins on their surface which normally protect them from being destroyed (a process called haemolysis) by the body's normal defence system. PNH is characterised by the presence of brownish urine in the early morning hours. The characteristic colour of urine is due to the presence of products from destroyed red cells. Patients have a low count of red blood cells, and may have blood clots in the large vessels. PNH is a life-threatening condition.

At the time of designation, PNH affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 4,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

*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. At the time of designation, this represented a population of 382,800,000 (Eurostat 2003).

There were no medicinal products authorised for the condition in the Community at the time of the submission of the orphan drug application. Bone marrow transplantation to replace the defective cells is the only curative therapy available to patients. This treatment is available to only a small proportion of patients since a suitable donor is required. Furthermore, transplantation maybe associated with substantial risks. 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.

In the human body there is a group of proteins called complement system, which have inflammatory properties and can destroy cells. Usually this system is activated as a defensive mechanism of the body. Proteins from the complement system are named with a “C” letter and a number. Normally each of these proteins can activate by cleavage other proteins. Eculizumab is an antibody that binds to human C5, a complement protein with capacity to start an inflammatory reaction in humans. After several steps this can result on the destruction of blood cells. It is expected that the binding of eculizumab to C5 will inhibit its cleavage into pro-inflammatory components, and therefore the subsequent cell lysis.

The effects of eculizumab were evaluated in experimental models.

At the time of the orphan drug designation clinical trials were ongoing.

At the time of submission of the orphan designation application, eculizumab had not been marketed anywhere worldwide for PNH or designated as 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 September 2003 recommending the granting of this designation.

Update: Eculizumab (Soliris) has been authorised in the EU since 20 June 2007 for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH).

Evidence of clinical benefit of Soliris in the treatment of patients with PNH is limited to patients with history of transfusions.

• 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 Community) 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.