Soliris (eculizumab) for paroxysmal nocturnal hemoglobinuria
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What is Soliris for PNH?
Soliris (eculizumab) is a monoclonal antibody that works to reduce the destruction of red blood cells in people with paroxysmal nocturnal hemoglobinuria (PNH). It was the first therapy approved to lessen blood cell destruction, a process known as hemolysis, in patients with PNH.
The intravenous (into-the-vein) therapy — developed by Alexion Pharmaceuticals, which was acquired in 2021 by AstraZeneca — also has shown evidence that it can prevent blood clotting and reduce the need for red blood cell transfusions in PNH patients.
Soliris also is approved by the U.S. Food and Drug Administration (FDA) for the treatment of myasthenia gravis (MG), atypical hemolytic uremic syndrome (aHUS), and neuromyelitis optica spectrum disorder (NMOSD).
Therapy Snapshot
| Brand Name: | Soliris |
| Chemical Name: | eculizumab |
| Usage: | to reduce the destruction of red blood cells (hemolysis) |
| Administration: | into-the-vein (intravenous) infusion |
How does Soliris work?
PNH is a rare disorder characterized by the early breakdown of red blood cells. Most cases of PNH result from mutations in the PIGA gene in hematopoietic stem cells, which are stem cells that give rise to all blood cells in the body.
The PIG gene family provides instructions for the production of proteins that are important for the formation of the glycosylphosphatidylinositol (GPI) anchor for membrane proteins on the surface of cells — the so-called GPI-anchored proteins. These proteins have several key roles.
Two important GPI-anchored proteins on the surface of red blood cells, called CD55 and CD59, are key inhibitors of the complement pathway, an important part of the immune system. In people with PNH, the lack of such proteins makes red blood cells susceptible to complement-mediated breakdown.
Eculizumab, the active ingredient in Soliris, works by specifically binding to the complement protein C5, preventing its cleavage into two forms called C5a and C5b, and ultimately blocking the action of the complement system.
The therapy therefore can reduce complement-driven hemolysis, and prevent related anemia, or a low red blood cells count.
Who with PNH can take Soliris?
The FDA approved Soliris for adults with PNH in March 2007 as a complement inhibitor to reduce hemolysis. According to the therapy’s developer, it is not known if Soliris is safe and effective in children with PNH.
Later in 2007, the therapy was approved in Europe for adults and children with PNH. In 2015, the European Commission extended the approval of Soliris to PNH patients without a history of transfusions — which often are required to treat anemia due to hemolysis.
Due to the risk of serious meningococcal infections associated with the treatment, Soliris is only available in the U.S. through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Healthcare providers prescribing Soliris must enroll in the program and be specifically certified.
Who should not take Soliris?
Soliris should not be taken by people who:
- have an unresolved serious infection due to the bacteria Neisseria meningitidis, which is known to cause meningitis and other forms of meningococcal disease
- are not vaccinated against Neisseria meningitidis, unless the risk of delaying Soliris treatment is greater than the risk of developing a meningococcal infection.
The prescribing label for Soliris has a boxed warning for serious, life-threatening meningococcal infections, as these have been reported in patients treated with the medication.
Meningococcal infections can become rapidly life-threatening or fatal if not identified and treated early. Patients should be carefully monitored for signs of infection.
How is Soliris administered in PNH?
Soliris is given via an infusion directly into the bloodstream (intravenous infusion). The treatment is available in single-dose vials containing a clear, colorless solution with 300 mg/30 mL (10 mg/mL) of eculizumab.
The dosing regimen for PNH patients ages 18 and older is:
- 600 mg weekly for the first four weeks
- a fifth dose of 900 mg one week later
- 900 mg every two weeks thereafter.
The infusion is typically given over 35 minutes in adult patients. If an adverse reaction occurs, the infusion may be slowed or stopped at the discretion of the healthcare team; if slowed, the total infusion time should not be more than two hours.
Patients should be carefully monitored for an infusion-related reaction for at least one hour after the end of the procedure.
Soliris in clinical trials
The approval of Soliris as a treatment to reduce hemolysis in PNH patients was supported by data from three Phase 3 clinical trials: TRIUMPH, SHEPHERD, and E05-001. In all three studies, Soliris was given at a 600 mg dose every week for 4 weeks, followed by a fifth dose of 900 mg a week later, and then 900 mg every other week thereafter.
TRIUMPH trial
The TRIUMPH study (NCT00122330) assessed the safety and efficacy of Soliris in adults with PNH. In total, 87 patients were randomized to receive Soliris or a placebo for 26 weeks (about six months).
Results showed that patients treated with Soliris had a significant reduction in hemolysis, resulting in improvements in anemia. This was measured by increased hemoglobin stabilization (49% vs. 0% in those receiving a placebo), and a reduced need for red blood cells transfusions — a median of zero units of packed cells in treated patients versus 10 units for those in the placebo group.
Patients treated with Soliris also showed a clinically significant improvement in their quality of life.
SHEPHERD trial
The safety of Soliris also was assessed over a period of 52 weeks (one year) in a multicenter, single-arm Phase 3 trial (NCT00122304) called SHEPHERD. It involved 97 patients who had received at least one transfusion in the 24 months (two years) before enrolling in the trial.
Trial data showed a decrease in hemolysis within blood vessels (intravascular hemolysis) that was sustained during the treatment period and resulted in a reduced need for transfusions and less fatigue.
E05-001 trial
The results of the previous trials were sustained in a long-term extension study (NCT00122317) known as E05-001, in which 187 PNH patients — each of whom had participated in prior PNH clinical trials — were enrolled. Most patients also were receiving anticoagulants.
These individuals continued to receive Soliris for a range of 10 months to 4.5 years (54 months).
All participants showed a reduction in intravascular hemolysis. Fewer blood clotting events were observed with Soliris when compared with before the treatment.
Common side effects of Soliris
The most common side effects related to treatment with Soliris in PNH patients are:
- headache
- cold (nasopharyngitis)
- back pain
- nausea.
Infections
The prescribing label warns for the risk of serious meningococcal infections in patients treated with Soliris. Patients who are being treated for this type of infection should stop treatment with Soliris.
Soliris should be administered with caution in those who have any other systemic infection.
Healthcare providers should follow the most updated Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with deficiency of the complement pathway.
Anyone with PNH without a history of meningococcal vaccination should be immunized at least two weeks before starting Soliris, unless the risk of delaying Soliris treatment is greater than the risk of developing a meningococcal infection. After vaccination, patients should still be monitored for possible symptoms of infection.
Injection-related reactions
People may develop infusion-related reactions while on Soliris, including hypersensitivity reactions. Patients should be monitored during infusion; if serious adverse reactions occur, the treatment should be stopped and appropriate supportive measures should be applied.
Use in pregnancy and breastfeeding
There is a lack of data on the use of Soliris in pregnant patients. Existing studies have not found adverse developmental outcomes. Animal studies, however, showed that a similar compound (an anti-C5 antibody) could cause harm to a developing fetus.
If left untreated, PNH poses risks to the mother and fetus.
It is not clear if Soliris can pass into breast milk or increase the risk of side effects in nursing infants. According to its prescribing label, Soliris should only be used during breastfeeding if the potential benefits outweigh the risks.
PNH News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Soliris
There is no known interaction between alcohol and Soliris. However, since alcohol can interfere with some medications and disease symptoms, it is recommended that patients talk about this issue with their healthcare providers.
The use of Soliris in pregnant women is not well-studied; however, a similar compound (an anti-C5 antibody) tested in animal models showed it could cause harm to a developing fetus. Pregnancy in women with untreated PNH is related to an increased risk of complications for both mother and fetus. Women who are pregnant or are planning to become pregnant should discuss this issue with their healthcare team.
Neither hair loss nor weight gain has been reported in clinical trials as side effects of Soliris treatment in patients with paroxysmal nocturnal hemoglobinuria. Patients are advised to speak with their healthcare provider if they experience any unusual symptoms while on the medication.
Patients with paroxysmal nocturnal hemoglobinuria may see results soon after starting treatment: The TRIUMPH trial showed that Soliris could reduce intravascular hemolysis in a week, and patients treated with the therapy reported improved health-related quality of life after 3 weeks. A significant reduction in hemolysis, which resulted in improvements in anemia and a reduced need for red blood cells transfusions, was evident with Soliris at six months after treatment start. However, each patient is unique and may have different disease manifestations and different responses to treatment. Therefore, a discussion with their healthcare team can help PNH patients understand how Soliris may help in their particular case.
Soliris was approved by the U.S. Food and Drug Administration (FDA) in March 2007 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). The therapy also is approved in the U.S. for atypical hemolytic uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorder.
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