Soliris (eculizumab) for paroxysmal nocturnal hemoglobinuria

Last updated June 10, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

 

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 red 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 — 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).

Some Soliris biosimilars are available. Biosimilars are products that contain a version of the same active ingredient that’s functionally equivalent to the reference biological product they are based on. Bkemv (eculizumab-aeeb), the first interchangeable biosimilar of Soliris to become available in the U.S., was approved in 2024 by the FDA to treat PNH and aHUS. Sold by Amgen, Bkemv is also available in Europe for the treatment of PNH, where it is marketed as Bekemv.

Therapy snapshot

Brand name:	Soliris
Chemical name:	Eculizumab
Usage:	Reduce the destruction of red blood cells (hemolysis)
Administration:	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 cell 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, making it the first therapy to be approved for the condition.

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 called Ultomiris and Soliris REMS. REMS stands for Risk Evaluation and Mitigation Strategy. Healthcare providers prescribing Soliris must enroll in the program and be specifically certified. Additionally, prescribers must inform patients of the potential risks of treatment and assess their vaccination status for meningococcal vaccines, ensuring they meet current recommendations before receiving treatment. The program also ensures only certified pharmacies can dispense Soliris.

Who should not take Soliris?

Soliris is contraindicated, or not recommended, for initiation in people who have an unresolved serious infection caused by the bacteria Neisseria meningitidis, which is known to cause meningitis and other forms of meningococcal disease.

The prescribing label for Soliris has a boxed warning for serious, life-threatening meningococcal infections, as these have been reported in patients treated with complement inhibitors. Meningococcal infections can rapidly become life-threatening or fatal if not identified and treated early. Patients should be carefully monitored for signs of infection.

The boxed warning also notes that patients should receive vaccination against meningococcal bacteria before starting treatment with Soliris — unless the risks of delaying treatment outweigh the risks of a serious infection. Patients should be monitored for early signs and symptoms of these infections and be evaluated immediately if an infection is suspected.

The safety and effectiveness of Soliris for the treatment of PNH in children have not been established.

How is Soliris administered in PNH?

Soliris is given via an infusion directly into the bloodstream. 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.

If Soliris treatment needs to be stopped, PNH patients should be monitored for signs of hemolysis for at least eight weeks.

The use of Soliris should not alter treatment with anticoagulant therapies. The effect of withdrawing anticoagulant therapies during Soliris treatment has not been established.

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 four 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 randomly received either 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 cell transfusions. A median of zero units of packed red blood cells was given to treated patients, compared with 10 units given to 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-like symptoms (nasopharyngitis)
• back pain
• nausea.

Serious meningococcal infections

The prescribing label for Soliris notes that the therapy can increase the risk of meningococcal infections, a type of bacterial infection that can be life-threatening and has been observed in both vaccinated and unvaccinated patients treated with complement inhibitors. Soliris should not be started in patients who have an unresolved serious infection caused by the bacteria Neisseria meningitidis, and should be given 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 for patients receiving a complement inhibitor.

Anyone with PNH without a history of meningococcal vaccination should be immunized for meningococcal bacteria (serogroups A, C, W, Y, and B) at least two weeks before starting Soliris, unless the risk of delaying Soliris treatment is greater than the risk of developing a meningococcal infection. If Soliris needs to be given before vaccination is up to date, the patient should also receive prophylactic (preventive) antibiotics to reduce the risk of bacterial infection, and the recommended vaccines should be given as soon as possible afterward.

Vaccination reduces the risk of meningococcal infection, but doesn’t totally eliminate it, so patients should still be monitored for possible symptoms of infection after being vaccinated. Patients should be informed of the signs and symptoms of such infections, and seek immediate medical care if these occur. If an infection is suspected, patients should be immediately evaluated and promptly treated.

If a serious infection develops, treatment with Soliris may be interrupted.

Other infections

Serious infections caused by other species of Neisseria bacteria, including disseminated gonococcal infections, have also been reported.

Patients treated with Soliris may be more susceptible to developing infections caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae. Vaccination to prevent infections caused by S. pneumoniae and H. influenzae should be administered according to ACIP recommendations.

Infusion-related reactions

People may develop infusion-related reactions while on Soliris, including hypersensitivity (allergic) 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 not much data on the use of Soliris in pregnant patients. An analysis of data from more than 300 pregnant women who had been exposed to Soliris did not show any major safety concerns, though the relatively small sample size makes it impossible to draw definitive conclusions. Animal studies, however, showed that a similar compound (an anti-C5 antibody) could cause harm to a developing fetus. It’s also important to consider that untreated PNH can pose a risk to both the mother and the developing fetus during pregnancy, so the potential benefits and risks of using Soliris during pregnancy should be carefully considered.

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.

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