Living with PNH in the UK

The following fact sheet was prepared by Dr. Dupe Elebute, Consultant at King’s College Hospital, Denmark Hill, London.

•    PNH is a chronic, life-threatening disease.

•    It is an acquired disorder affecting the haemopoietic stem cell. There are no reports of inherited or familial cases of PNH.

•    It affects patients of all ages but diagnosis is most common in the 4th decade of life. It affects both sexes equally.

•    It is caused by somatic mutation of the phosphatidylinositol glycan class A gene (PIG-A) which is located on the X chromosome (Xp22).

•    Mutation of the PIG-A gene limits or prevents synthesis of the glycosylphosphatidylinositol (GPI) anchor which normally holds many membrane proteins to the cell surface.

•    Partial or total deficiency of the GPI anchor on red blood cells results in increased susceptibility to breakdown (or lysis) by complement, leading to the classic intravascular haemolysis seen in this condition.

•    The main symptoms and signs of PNH include:

• Anaemia
• Chronic debilitating fatigue
• Breathlessness
• Angina chest pain
• Renal (kidney) failure

•    Other symptoms include:

• Oesophageal spasm
• Dysphagia (difficulty with swallowing)
• Erectile dysfunction
• Abdominal pain (may herald hepatic vein thrombosis (blood clots), Budd Chiari syndrome, which if not promptly recognised could be life threatening)

•    There is a high risk of life-threatening thrombosis in up to 30% of PNH patients, a 10% risk of development of bone marrow failure (Aplastic Anaemia) and a 1-5% chance of developing acute myeloid leukaemia (AML).

•    Median survival from the time of diagnosis is 10-15 years with thrombosis being the major cause of death.

•    There is a significantly increased risk of thrombosis and other complications during pregnancy.

•    Standard treatment for this condition prior to 2007 was mainly supportive including regular blood transfusions and immunosuppressive drugs such as steroids and androgens (a male hormone) with varying response and risk of long-term side effects.

•    Allogeneic bone marrow transplants (transplant from a brother or sister or volunteer donor) provide the only potential curative treatment for PNH but is associated with such significant morbidity and mortality that it is only recommended for patients who have developed serious complications such as thrombosis or bone marrow failure.

•    Eculizumab (Soliris ®) a humanized monoclonal antibody which targets complement C5 was licensed in 2007 as the first available drug therapy for PNH. It has been shown in well-designed multi-centre studies to prevent haemolysis and significantly reduce transfusion requirements in PNH patients. Soliris ® has also been shown to reduce the incidence of thrombosis in PNH.

•    The United Kingdom contributed the greatest number of patients to the clinical trials of Eculizumab, demonstrating the significant expertise and research capabilities of the UK.

•    Recently, the National Specialised Commissioning Group (NSCG) turned down an application for national commissioning of Eculizumab (Soliris ®) for the treatment of PNH.

•    PNH patients in North America, Australia and other EU countries including France, Germany, Spain, Italy, Greece and Turkey have access to Soliris ®.

•    Inequality of access according to location now exists across the UK with PNH patients residing in 2 SHAs (Yorkshire and Humberside SHA and South East Coast SHA) having access to the drug whilst patients in the other 8 do not have access. Furthermore, patients in Scotland have access to the drug.