Paroxysmal nocturnal haemoglobinuria (PNH) is a rare blood disorder where the body’s own immune system turns against its red blood cells, leading to serious complications including life-threatening blood clots. Modern treatments now allow many patients to live full lives, though managing this condition requires careful attention and ongoing medical support.
Understanding How Treatment Approaches Work for PNH
The primary goal when treating paroxysmal nocturnal haemoglobinuria is to stop the destruction of red blood cells, prevent dangerous blood clots, and improve patients’ ability to carry out everyday activities. This rare condition affects only about 6 in every million people each year, and because it varies greatly from person to person, treatment must be tailored to each individual’s specific needs and symptoms.[1]
Treatment strategies depend on several factors, including how severe the symptoms are, whether blood clots have occurred, and how much the disease is affecting the patient’s quality of life. Some people with very small amounts of abnormal cells may need little or no treatment at all, while others require intensive medical intervention to manage serious complications.[5]
There are approved therapies that medical societies recommend based on years of clinical experience, and there is also active research into new medications and approaches that might offer even better outcomes. Healthcare providers consider both standard treatments and emerging therapies when developing a care plan for someone with PNH.[8]
The ultimate aim is not just to control symptoms but to reduce the risk of life-threatening complications like blood clots, which historically were the leading cause of death in people with this condition. With appropriate treatment, many patients can now expect a life expectancy similar to people without PNH.[4]
Standard Medical Treatments for Paroxysmal Nocturnal Haemoglobinuria
The main treatment approach for PNH involves using medications called complement inhibitors, which are special proteins designed to stop the immune system from destroying red blood cells. The complement system is part of the body’s natural defence mechanism, but in PNH, it mistakenly attacks the patient’s own blood cells because they lack protective proteins on their surface.[1]
Eculizumab, marketed under the brand name Soliris, was the first drug specifically approved for treating PNH, receiving licensing in Europe in 2007. This medication is a monoclonal antibody, which means it’s a laboratory-made protein that targets a specific part of the immune system. Eculizumab attaches to a protein called C5 in the complement system and blocks it, preventing the chain of events that leads to red blood cell destruction.[14]
Eculizumab is given through an intravenous infusion, meaning it’s delivered directly into a vein. Patients typically receive treatment once every two weeks on an ongoing basis. In many countries, including the United Kingdom, nurses can administer this medication at the patient’s home, making the treatment more convenient. Each infusion usually takes about 30 minutes, with the nurse monitoring blood pressure and temperature before and after to watch for any reactions.[14]
Another complement inhibitor called ravulizumab, sold as Ultomiris, works similarly to eculizumab by blocking the C5 protein. The key difference is that ravulizumab lasts longer in the body, so patients only need infusions every eight weeks instead of every two weeks. This reduced treatment frequency can significantly improve quality of life by reducing the burden of frequent hospital or clinic visits. Ravulizumab was approved in the United States in December 2018 and in Europe in July 2019.[14]
Pegcetacoplan, known as Empaveli, represents a different approach. Instead of blocking C5, this medication targets C3, which is another protein in the complement system. By blocking at an earlier point in the complement cascade, pegcetacoplan may help patients who still experience red blood cell destruction despite treatment with C5 inhibitors. It’s administered as a subcutaneous infusion (under the skin) twice weekly.[10]
A newer oral medication called iptacopan was approved by the U.S. Food and Drug Administration in 2023. This drug inhibits factor B, a component of the alternative complement pathway. The advantage of iptacopan is that it comes as a pill rather than an infusion, which many patients find more convenient. It’s indicated as monotherapy, meaning it can be used as the sole treatment for PNH.[10]
Danicopan is a selective inhibitor of complement factor D that received FDA approval in 2024. This medication is specifically designed to be added to C5 inhibitor therapy for patients who continue to experience red blood cell destruction outside the blood vessels, known as extravascular haemolysis. Some patients treated with C5 inhibitors still have anaemia and need blood transfusions because red blood cells are being destroyed in the liver and spleen rather than in the bloodstream. Danicopan helps address this ongoing problem.[10]
These complement inhibitor medications don’t cure PNH, but they dramatically reduce symptoms and most importantly prevent blood clots, which used to be the main cause of death in PNH patients. Clinical guidelines recommend starting complement inhibitor therapy for patients with haemolysis causing clinical symptoms or for those with blood clots. The treatment continues indefinitely, as stopping it usually leads to a return of symptoms.[8]
For patients who develop blood clots, immediate treatment with anticoagulants (blood thinners) is essential. Initially, a medication called heparin is used, followed by long-term treatment with oral anticoagulants such as warfarin. Patients starting complement inhibitor therapy who aren’t already on anticoagulants may begin this medication to prevent clots. However, blood thinners carry their own risks, particularly increased bleeding, so patients must be carefully monitored.[10]
Some patients may receive corticosteroids like prednisone to help control haemolysis, typically at doses of 20-40 mg daily during episodes of red blood cell breakdown. However, steroids only provide modest benefit and can cause significant side effects with long-term use, including weight gain, high blood pressure, diabetes, and weakened bones. For this reason, they’re used cautiously and generally in conjunction with other treatments.[10]
Blood transfusions are sometimes necessary when anaemia becomes severe and causes symptoms like extreme fatigue, shortness of breath, or rapid heartbeat. Transfusions provide temporary relief by increasing the number of red blood cells, but they don’t address the underlying problem. Some patients require regular transfusions to maintain adequate blood counts, though the goal of complement inhibitor therapy is to reduce or eliminate this need.[11]
Patients may also receive iron and folic acid supplements to support the production of new red blood cells. When red blood cells break down in PNH, iron is lost through the kidneys into the urine, potentially leading to iron deficiency. Folic acid is a vitamin that helps the bone marrow produce new blood cells. These supplements help the body compensate for ongoing cell destruction.[12]
The only treatment that can truly cure PNH is an allogeneic bone marrow transplant, also called a stem cell transplant. This procedure replaces the patient’s abnormal blood-forming stem cells with healthy ones from a donor, usually a close relative. However, bone marrow transplantation carries significant risks, including severe infections, organ damage, and graft-versus-host disease, where the donor cells attack the patient’s body. Historical data showed a 42 percent death rate at 12 months among PNH patients who received transplants between 1988 and 2006. Because of these serious risks, transplantation is typically reserved only for patients with severe bone marrow failure or life-threatening complications who don’t respond to other treatments.[8]
Innovative Treatments Being Tested in Clinical Trials
Researchers continue to develop new therapies that might offer better outcomes, fewer side effects, or more convenient administration compared to current treatments. Clinical trials are studies where new medications or treatment approaches are tested in volunteer patients to determine if they’re safe and effective. Understanding the different phases of clinical trials helps patients appreciate what these studies aim to discover.[11]
Phase I trials focus primarily on safety. Researchers give the new treatment to a small number of people to find out what side effects occur and determine safe dosing ranges. Phase I studies typically don’t provide information about whether the treatment works, only whether it appears safe enough to continue testing.
Phase II trials examine whether the treatment actually helps patients. These studies involve more participants and measure specific outcomes like reduction in symptoms, improvement in blood counts, or prevention of complications. Researchers also continue monitoring for side effects.
Phase III trials compare the new treatment directly to the current standard treatment or to placebo. These are large studies involving hundreds of patients, often conducted at multiple locations across different countries. Phase III results determine whether a new drug will be approved by regulatory agencies like the FDA or European Medicines Agency.
Crovalimab is an experimental C5 complement inhibitor being studied as an alternative to eculizumab and ravulizumab. Like these drugs, crovalimab is a monoclonal antibody that blocks the cleavage of C5, preventing complement activation. Early clinical trials have shown promising results, with patients experiencing control of haemolysis and improvement in symptoms. One potential advantage of crovalimab is its dosing schedule, which researchers are exploring to optimize patient convenience while maintaining effectiveness.[11]
Clinical trials for crovalimab have been conducted in multiple countries including the United States, Europe, and Asia. Patients eligible for these studies typically must have confirmed PNH diagnosis with evidence of active haemolysis. Some trials enrolled patients who had never received complement inhibitor therapy before, while others studied patients switching from eculizumab or ravulizumab to crovalimab.
Next-generation complement inhibitors are being designed to address some limitations of current therapies. Some patients treated with C5 inhibitors continue to experience anaemia and need blood transfusions because red blood cells are still being destroyed, just through a different mechanism called extravascular haemolysis. Newer drugs targeting different points in the complement pathway may provide more complete protection.[10]
Researchers are investigating treatments that block complement activation at earlier stages, before the cascade reaches C5. These approaches might prevent both intravascular haemolysis (red blood cell destruction in the bloodstream) and extravascular haemolysis (destruction in organs like the liver and spleen). Clinical trials are examining whether these earlier-acting inhibitors lead to better red blood cell survival and reduced transfusion needs.
Some clinical studies focus on understanding why certain patients don’t respond as well to existing treatments. Genetic variations in complement proteins can affect how well medications work. Research has identified polymorphisms (natural variations) in the complement receptor 1 gene that may influence treatment response. Understanding these genetic factors could help doctors predict which patients will benefit most from specific therapies and potentially develop personalized treatment approaches.[10]
Combination therapies are also being explored in clinical trials. The approval of danicopan as an add-on treatment to C5 inhibitors represents this approach. Researchers are studying whether combining drugs that block different parts of the complement system or using complement inhibitors together with other medications might provide better disease control than any single drug alone.
Clinical trials specifically examine quality of life as an outcome measure, not just blood test results. Living with PNH affects patients’ ability to work, care for family members, engage in social activities, and maintain mental health. New treatments are being evaluated based on whether they help patients feel better and do more, not just whether they improve laboratory values. Patient-reported outcome questionnaires help researchers understand the real-world impact of investigational therapies.[8]
Clinical trial locations vary depending on the specific study. Many trials for PNH are conducted at specialized haematology centres in the United States, major European cities, and increasingly in Asia and other regions. Patients interested in clinical trials should discuss options with their haematologist, who can help determine eligibility and provide information about studies currently enrolling participants.
Eligibility criteria for PNH clinical trials typically include confirmed diagnosis through flow cytometry testing, evidence of haemolysis, and specific requirements regarding previous treatments. Some trials seek patients who have never been treated with complement inhibitors, while others specifically study patients who have been on these medications but continue to have symptoms. Age restrictions, pregnancy status, and other medical conditions also affect eligibility.
Most common treatment methods
- Complement inhibitor therapy
- Eculizumab (Soliris) – monoclonal antibody given by intravenous infusion every 2 weeks, blocks C5 protein to prevent red blood cell destruction[14]
- Ravulizumab (Ultomiris) – longer-acting C5 inhibitor requiring infusions only every 8 weeks[14]
- Pegcetacoplan (Empaveli) – targets C3 protein, given subcutaneously twice weekly for patients with ongoing haemolysis[10]
- Iptacopan – oral factor B inhibitor approved in 2023, can be used as monotherapy[10]
- Danicopan – factor D inhibitor approved in 2024 as add-on to C5 inhibitor therapy for extravascular haemolysis[10]
- Crovalimab – experimental C5 inhibitor being studied in clinical trials[11]
- Supportive care
- Immunosuppressive therapy
- Curative treatment
- Allogeneic bone marrow transplant (stem cell transplant) – replaces abnormal stem cells with healthy donor cells, only cure but carries significant risks[8]
