Complement Inhibition
Ravulizumab
Ravulizumab (or Ultomiris) is an intravenous infusion that is administered every 8 weeks in the long term. The first 2 doses are given 2 weeks apart. Ravulizumab blocks the activation of complement and therefore protects the PNH cells from destruction or stimulation.
Ravulizumab works in the same way as Eculizumab, the structure of the drug has been changed to create a longer-lasting treatment. As soon as Ravulizumab therapy is stopped, complement will become active and the PNH cells that were previously protected will be vulnerable to complement attack again. It is therefore usual that Ravulizumab is a treatment that needs to be given lifelong.
Ravulizumab has been proven to reduce the symptoms experienced in PNH and has been shown to improve people’s quality of life.
It also reduces the risks of many of the complications of PNH, such as thrombosis, renal failure or pulmonary hypertension (high blood pressure in the lungs).
Ravulizumab remains in the body for longer than Eculizumab so is, therefore, the preferred treatment option for patients outside a clinical trial who require complement inhibitor.
Eculizumab
Eculizumab (or Soliris) is an intravenous infusion that is administered every 2 weeks in the long term. Eculizumab blocks the activation of complement and therefore protects the PNH cells from destruction or stimulation. As soon as Eculizumab therapy is stopped, complement will become active and the PNH cells that were previously protected will be vulnerable to complement attack again. It is therefore usual that Eculizumab is a treatment that needs to be given lifelong.
Eculizumab has been proven to reduce the symptoms experienced in PNH and has been shown to improve people’s quality of life. It also reduces the risks of many of the complications of PNH, such as thrombosis, renal failure or pulmonary hypertension (high blood pressure in the lungs). It has also therefore improved life expectancy in certain groups of patients with PNH.
Bekemv and Epysqli now developed for Eculizumab equivalent as proven in clinical trials and the response is the same as Eculizumab. The NHS is committed to using biosimilars where appropriate.
Crovalimab
Crovalimab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein, thereby reducing haemolysis
It is recommended for people who have haemolysis with clinical symptoms indicating high disease activity.
The active substance crovalimab, attaches to the complement 5 (C5) protein, which is a part of the body’s defence system called the ‘complement system’. By doing so, it blocks activation of C5, which prevents the immune system from attacking and damaging red blood cells, thereby reducing the breakdown of red blood cells. This helps to reduce the symptoms of PNH and the number of blood transfusions required.
Crovalimab is given as an intravenous infusion (drip into a vein) for the first dose and thereafter, as an injection under the skin (subcutaneous injection).
Pegcetacoplan
Pegcetacoplan is a C3 inhibitor, and thus considered a proximal complement inhibitor. It is currently approved for patients experiencing Anaemia after 3 months on Eculizumab or Ravulizumab. It is given by a subcutaneous infusion twice a week at home.
In the clinical trials, patients on Eculizumab who were anaemic had an improvement of their haemoglobin by 3.8g/dl. Pegcetacoplan has been proven to reduce symptoms experienced in PNH, and also improve the anaemia caused by extravascular haemolysis.
Your PNH team will discuss whether you are eligible for treatment.
Iptacopan
Iptacopan has recently received approval in England and Wales for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).
It is an oral medicine used on its own.
It is indicated for patients who have not previously undergone treatment for PNH, as well as those who are currently receiving complement inhibition therapy.
Iptacopan targets a protein called Factor B, which is part of body’s immune system called “complement system”.
As a factor B inhibitor, Iptacopan functions as a proximal complement inhibitor, specifically targeting factor B within the complement pathway (see diagram below). This mechanism allows it to effectively manage both intravascular and prevent extravascular haemolysis associated with PNH.
The anticipated outcomes for patients using Iptacopan include improved haemoglobin levels without the need for blood transfusions, as well as a reduction in symptoms such as tiredness and fatigue. These improvements are expected to enhance the overall quality of life for individuals diagnosed with PNH.
Danicopan
Danicopan is an oral tablet medication taken three times per day (every 8 hours). It can be taken with or without food. It has been developed to treat PNH by blocking a protein called factor D in the complement system and is taken alongside your usual IV treatment Eculizumab and Ravulizumab.
Danicopan is an add-on therapy available for patients who are already on a Complement inhibitor (Eculizumab/Ravulizumab) and are experiencing extravascular haemolysis, causing anaemia. It is likely to benefit patients that have developed anaemia by working on the Factor D pathway which inhibits extravascular haemolysis.