Soliris (eculizumab) for myasthenia gravis

Last updated Nov. 1, 2024, by Joana Carvalho, PhD
Fact-checked by Ines Martins, PhD

What is Soliris for myasthenia gravis?

Soliris (eculizumab) is an infusion therapy approved for the treatment of adults with generalized myasthenia gravis (gMG) who are positive for antibodies against the acetylcholine receptor (AChR), the most common type of MG-causing antibody.

Administered via an infusion into a vein, or intravenously, the therapy is a complement inhibitor that helps ease gMG symptoms and reduce their impact on the ability to perform daily activities.

Originally developed by Alexion Pharmaceuticals, which was acquired by Astrazeneca in 2021, the medication is also approved for treating paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and neuromyelitis optica spectrum disorder.

Therapy snapshot

How does Soliris work?

Myasthenia gravis, known as MG, is an autoimmune disease wherein a person’s immune system erroneously attacks proteins involved in the communication between nerves and muscles, leading to symptoms of muscle weakness and fatigue.

This immune attack is driven by self-reactive antibodies. In about 80% of MG cases, these antibodies target the AChR, which plays a key role in nerve-muscle communication and muscle contraction.

When anti-AChR antibodies bind to their target, they can activate a part of the immune system called the complement system, which consists of a group of proteins normally found in the blood in an inactive state.

In response to certain stimuli, such as an infection or the autoimmune attack that drives MG, however, the complement system becomes activated, with proteins triggering each other in a cascade. This is believed to contribute to the damaging immune response seen in MG.

Soliris is designed to block the complement cascade. It specifically binds to a complement protein called C5, preventing its cleavage into other complement components — C5a and C5b — and ultimately blocking complement activation.

This mechanism of action is identical to that of Ultomiris (ravulizumab-cwvz), another C5 inhibitor also developed by Alexion that was more recently approved for gMG. Ultomiris was slightly modified to be more stable and last longer than Soliris, allowing for less frequent dosing.

Who with myasthenia gravis can take Soliris?

Soliris was approved by the U.S. Food and Drug Administration in October 2017 to treat adults with gMG who are positive for anti-AChR antibodies. Its approval was the first in the U.S. for the condition in more than 60 years.

The medication is associated with an increased risk of serious meningococcal infections, which can become rapidly life-threatening or fatal if not detected and treated early. For this reason, Soliris is only available in the U.S. through a restricted access program called Ultomiris and Soliris REMS (Risk Evaluation and Mitigation Strategy), which ensures that only certified healthcare professionals and pharmacies can prescribe and dispense it.

Besides having to enroll in REMS, prescribers must inform patients of the risks of serious meningococcal infection and assess their vaccination status for meningococcal vaccines, making sure they meet current recommendations before receiving treatment.

Soliris is also approved in Europe for adults and children, ages 6-17, with refractory gMG, meaning those who failed to respond to conventional therapies, and anti-AChR antibodies.

The medication is approved in Japan f or anti-AChR positive adults and children whose symptoms are not effectively controlled with high-dose intravenous immunoglobulin therapy or plasmapheresis, also called plasma exchange.

Who should not take Soliris?

Soliris is not recommended to be started in patients who have serious and unresolved infections caused by the bacteria Neisseria meningitidis, which can cause a serious condition called meningococcal disease.

The prescribing information for Soliris carries a boxed warning for serious and life-threatening meningococcal infections, which have occurred in patients treated with complement inhibitors. Patients should be monitored for early signs and symptoms of these infections and evaluated immediately if an infection is suspected.

The boxed warning also notes that patients should receive vaccination against meningococcal bacteria before starting treatment with Soliris, except if the risks of postponing treatment outweigh the potential risks of developing a meningococcal infection.

How is Soliris administered in myasthenia gravis?

Soliris is administered via intravenous infusions by a trained healthcare professional at a recommended maintenance dose of 1,200 mg, every two weeks.

For those initiating treatment, there is an initial loading period of five weekly doses. The first four doses deliver 900 mg of the medication and the fifth delivers the recommended 1,200 mg maintenance dose a week later. From that point on, patients receive the recommended 1,200 mg maintenance dose every two weeks. Soliris should be administered at the recommended dosing time points, or within two days of those scheduled timepoints.

If patients also are receiving treatment with plasma exchange or intravenous immunoglobulin, which can decrease the amount of Soliris in circulation in the body, supplemental doses of the medication might be required.

Soliris infusions are typically given over 35 minutes, although some can take up to two hours if patients experience infusion-related reactions. After the infusion, patients should be monitored for at least one hour for signs or symptoms of infusion reactions.

Soliris in clinical trials

Soliris’ regulatory approval for adults in the U.S. was based on data from a Phase 3 trial called REGAIN (NCT01997229), completed in 2016.

REGAIN trial

Sponsored by Alexion, REGAIN enrolled 125 adults with anti-AChR-positive gMG, who had mild to severe muscle weakness and had failed to respond to immunosuppressive treatments — meaning those with refractory disease.

Participants were randomly assigned to receive either Soliris or a placebo for 26 weeks, or about six months. Soliris was given at the now approved regimen: patients initially received four weekly 900 mg doses of the medication, followed by a 1,200 mg dose one week later, and every-two-week 1,200 mg doses thereafter.

The trial’s main goal was to assess changes in MG-Activities of Daily Living (MG-ADL) scores, which assess patient-reported symptom severity. This scale ranges from 0 to 24, and higher scores indicate more severe symptoms with a greater impact on the ability to function in daily life.

Top-line results announced in 2016 showed the primary goal was not met. While Soliris-treated participants tended to have lower MG-ADL scores at the trial’s conclusion, indicating less severe symptoms, the difference between the groups did not reach statistical significance.

However, Soliris significantly outperformed the placebo on the Quantitative MG (QMG) scale, a clinician-reported measure of disease severity. Also, significantly more patients on Soliris than those on the placebo achieved clinically meaningful reductions in both MG-ADL and QMG scores after 26 weeks.

The treatment was generally safe. The most common adverse events were headache, upper respiratory tract infection, and the common cold, which were mostly mild to moderate in severity and deemed unrelated to Soliris.

Open-label extension

Of the 118 participants who completed REGAIN, 117 chose to enroll in an open-label extension study (NCT02301624), in which all received Soliris for up to four years and were monitored for long-term safety and efficacy.

Data from the extension study generally showed that the benefits of Soliris seen in the original trial were sustained with prolonged treatment. After a median treatment duration of 22.7 months, 74.1% of patients had experienced clinical improvements compared with the start of REGAIN, and 56% had achieved minimal manifestations of the disease, or pharmacological remission.

Compared with the year before entering REGAIN, patients also saw a 75.2% reduction in the rate of disease exacerbations, or episodes of sudden symptom worsening. They also had a more than 80% reduction in hospital admissions. Moreover, the use of rescue therapies also was significantly lowered.

Other analyses of data from the two studies showed Soliris led to sustained improvements in muscle strength and was effective across ethnicities. Treatment with Soliris also did not increase the risk of infection and lowered the need for other immune-suppressing medicines.

A post hoc analysis, or one done after the trials were completed, demonstrated Soliris also was effective in participants who had failed to respond to rituximab, which is sometimes used off-label in MG.

Data also indicated that most patients responded to Soliris within three months of starting treatment, however, for more than 15% of participants, a response didn’t become evident until some time later.

Results of real-world studies conducted in the U.S. and Japan have generally been consistent with what was found in clinical trials, demonstrating the therapy’s safety and efficacy outside the clinic.

Phase 3 trial in children

Soliris’ label expansion to include children and adolescents in Europe and Japan was backed by data from an open-label Phase 3 clinical trial (NCT03759366) that enrolled 11 children and adolescents, ages 6 to 17, with AChR-positive refractory gMG. Participants were treated with weight-based doses of Soliris for 26 weeks, or about six months.

The study’s main goal was to assess changes in the QMG scores from the study’s start to week 26. Changes in MG-ADL scores also were evaluated as a key secondary goal.

Results showed QMG scores dropped by a mean of 5.8 points and MG-ADL scores decreased by a mean of 2.3 points over six months, suggesting less severe disease. Improvements in these and other clinical outcomes became apparent as early as one week after treatment initiation and were sustained through week 26.

The therapy’s safety profile in children was consistent with its profile in adult patients. The most common side effects observed in the study were headache and cold-like symptoms.

Common side effects of Soliris

The most common side effect of Soliris reported in clinical trials of gMG patients was musculoskeletal pain, or pain involving the bones, muscles, joints, ligaments, and tendons.

Serious meningococcal infections

Soliris carries a boxed warning noting the therapy can increase the risk of serious meningococcal infections, which can rapidly become life-threatening or fatal if not detected and treated early. These bacterial infections have 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 to those who have any other systemic infection.

People starting on this medication should be vaccinated according to current recommendations. Meningococcal vaccination for bacteria belonging to serogroups A, C, W, Y, and B should be completed at least two weeks beforeinitiating  treatment, unless the risks of delaying treatment outweigh the potential risks of meningococcal infections. In cases where Soliris needs to be given before a vaccination is up to date, patients should also be given prophylactic (preventive) antibiotics to reduce the risk of bacterial infection, and the recommended vaccines should be given as soon as possible thereafter.

While such vaccines reduce the risk of meningococcal infections, they do not completely eliminate it. Therefore, patients should be routinely monitored for early signs of infections, and promptly treated if an infection develops.

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.

Because Soliris dampens immune responses, patients receiving the therapy may be more susceptible to developing infections, particularly those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Vaccination to prevent infections caused by S. pneumoniae and H. influenzae should be administered according to current recommendations. Even patients who develop antibodies following vaccination against these bacteria are at an increased risk of developing infections while receiving Soliris, so caution is advised.

Infusion-related reactions

Soliris can cause infusion-related reactions, which can include allergic reactions, such as anaphylaxis. No patients have discontinued the medication in clinical trials due to infusion reactions, however. If patients do exhibit cardiovascular or respiratory distress, Soliris should be interrupted and patients should receive appropriate supportive measures.

Use in pregnancy and breastfeeding

There is limited data regarding the use of Soliris during pregnancy. Research in animals suggests it may cause damage to the developing fetus, but data from more than 300 women exposed to Soliris during pregnancy raised no safety issues.

It also is not known if Soliris can be found in breast milk and whether it has any impact on nursing infants. Those who plan to breastfeed should inform their healthcare team and carefully weigh the potential benefits and risks of using the medication while breastfeeding.

Myasthenia Gravis 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.