There are different treatments which those living with PNH may require. Some people, especially those with a small PNH clone may require little or no treatment.
“Soliris” has been licensed for use in Europe since 2007 and it is administered by way of intravenous infusion once every two weeks on an ongoing basis.
Soliris is a monoclonal antibody which blocks the complement part of the immune system. It is designed to attach to the C5 protein, which is part of the complement system and by doing so, the medicine blocks its effect and thereby reduces the destruction of red blood cells. It is not curative but dramatically reduces symptoms, the most significant of which is the occurrence of blood clots (which used to be the main cause of death in patients) and allows patients to have the life expectancy of someone without PNH. It has also more recently been used safely in pregnancy, which previously had to be avoided by PNH patients due to the risk of blood clots.
In England and Wales, the criteria for patients being able to be treated with eculizumab can be found here.
Although available in approximately 40 countries, unfortunately, this treatment is not available to all PNH patients globally due to its very high cost (approximately £300,000 per person per year). Bone marrow transplants can cure PNH but are rarely used due to the risk of severe complications.
Terminal complement (which eculizumab prevents from forming) is required to prevent Neisseria Meningitidis which is a bacteria which can cause meningitis and other forms of meningococcal disease. Therefore patients treated with eculizumab are more likely to develop infections caused by the Neisseria group of bacteria. To reduce this risk, all PNH patients starting treatment with eculizumab are vaccinated with a vaccine against the meningococcal strains A, C, W and Y. The vaccine against serotype B (the most common serotype in the UK) is licensed and is used in patients treated with eculizumab. Patients are also advised to take 500mg of either penicillin or erythromycin twice daily as a prophylactic antibiotic to protect them from infection.
Patients treated with eculizumab are provided with a patient safety card to carry with them at all times which states the symptoms of meningitis and tells them what to do if they experience any of these symptoms.
In the UK, eculizimab is usually administered at patients’ homes by homecare nurses.
The nurse attends a patient’s home with the medication (or it is delivered separately and kept in the fridge) and administers an intravenous line into a vein and flushes the line with saline. The prescribed amount of eculizumab is then mixed with saline according to the prescription and this is then usually administered over a 30 minute period. After the eculizumab has been infused, the line is then flushed with saline again. Blood pressure and temperature are taken before and after the infusion in case there is any change which may indicate an adverse reaction.
Ravulizumab was licensed for use in adults with PNH in the United States of America (by the U.S Food and Drug Administration) in December 2018 and in Europe (by the European Medicines Agency) in July 2019. Ravulizumab has recently (15 April 2021) been recommended by the National Institute for Health and Care Excellence (NICE) as an option for treating paroxysmal nocturnal haemoglobinuria in adults:
• with haemolysis with clinical symptoms suggesting high disease activity, or
• whose disease is clinically stable after having eculizumab for at least 6 months.
Read NICE’s Guidance on the use of ravulizumab for patients meeting these criteria.
To read the Final Appraisal document please see here.
Like Soliris, Ravulizumab is also a monoclonal antibody which blocks the complement part of the immune system (also by attaching to C5). It is delivered by 8 weekly infusion into the vein on an ongoing basis.
The PNH National Service is currently making arrangements for all eligible patients to be moved from eculizumab to ravulizumab.
To hear Dr Austin Kulasekararaj discussing Ravulizumab please watch this video (2018)
Pegcetacoplan is a C3 inhibitor which has been trialled in PNH patients. It is delivered by a sub-cutaneous injection twice per week.
A recent article in the prestigious journal ′"New England Journal of Medicine" publishing the findings of the phase 3 study of pegcetacoplan (or APL2). C3 and C5 are proteins which are part of the complement system (complement system: the congenital immune system of the body) and the drugs interrupt the complement cascade which attacks the PNH affected blood cells.
This study compared the C3 inhibitor Pegcetacoplan (or APL2) to eculizumab and found that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients by providing broad hemolysis control, including control of intravascular and extravascular hemolysis. C5 inhibitors such as eculizumab and ravulizumab don’t control extravascular hemolysis.
Marketing applications (which licence drugs to be used) for Pegcetacoplan for the treatment of PNH are under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA granted this application Priority Review designation and set a target action date of May 14, 2021. An opinion from the EMA Committee for Medicinal Products for Human Use (CHMP) is expected in 2021.
Pending licensing, the NICE process to appraise Pegcetacoplan for payment (for use in adults with PNH whose anaemia is not controlled after treatment with a C5 complement inhibitor) has begun and PNH Support has been invited to make submissions by 24 June 2021.
Unfortunately the full publication of this article is behind a paywall but you can read about it in summary here.
Hear Professor Peter Hillmen discuss the Phase III study evaluating the efficacy and safety of APL-2 (Pegcetacoplan) here (2020)
Other New Drug Development
There are a number of other drugs in development to treat PNH (including biosimilars) and they vary in the way they are delivered i.e. pill, daily injection, 8 weekly infusion. If you are interested in taking part in a clinical trial, please speak to your haematologist or your clinical nurse specialist at your PNH National Service Centre.
All clinical trials which are currently recruiting are listed in the Clinical Trials Register which you can access here. In the search box, type “PNH" into “Condition or disease" and the relevant country into “Country".
Other Supportive treatments for PNH
Allogeneic Bone Marrow Transplant
It is not common for this treatment to be recommended for PNH patients unless there is a severe bone marrow failure co-existing with PNH. It has many significant complications which may occur in some patients.
Some patients take medication to thin their blood (such as warfarin or heparin) to reduce the risk of developing blood clots.
A red blood cell transfusions can alleviate some of the symptoms experienced with PNH, including anaemia. A red blood cell transfusion can usually be carried out in an outpatient clinic. Once your blood type is cross-matched for antibodies, one unit of blood takes approximately two hours to transfuse into your body. This will usually alleviate the symptoms resulting from anaemia and haemolysis for a period of time (which differs for each person).
Folic acid is a vitamin which the bone marrow needs to help it produce blood cells. This can be taken in tablet form.
Iron Supplements and Iron Removal
Iron levels can be both too high or too low in PNH and can depend on what other treatment someone is having. Some patients may need to take iron supplements such as ferrous sulphate and others may need to take medication to reduce the iron in their bodies.