Soliris (eculizumab) for myasthenia gravis

Last updated Feb. 1, 2024, by Inês Martins, PhD
Fact-checked by Joana Carvalho, 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 — the most common type of MG-causing antibody. It is designed to lessen the key gMG symptom of increasing muscle weakness.

Originally developed by Alexion Pharmaceuticals, which was acquired by AstraZeneca in 2021, the medication is a complement inhibitor that helps ease gMG symptoms and reduce their impact on patients’ ability to perform daily activities.

Soliris also is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and neuromyelitis optica spectrum disorder (NMOSD).

Therapy snapshot

How does Soliris work?

Myasthenia gravis, known as MG, is an autoimmune disease in which 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 acetylcholine receptor, which plays a key role in nerve-muscle communication and muscle contraction, and are called anti-AChR antibodies.

When these antibodies bind to their target, they can activate a part of the immune system called the complement system. This consists of a group of proteins that normally are found in the blood in an inactive state.

However, in response to certain stimuli, such as an infection or the autoimmune attack that drives MG, 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 in the body than Soliris, thus allowing for less frequent dosing.

Who with MG 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 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 Soliris REMS (Risk Evaluation and Mitigation Strategy), which ensures that only certified healthcare professionals can prescribe it.

Soliris also was approved in Europe in August 2017 for anti-AChR positive gMG patients with refractory disease, meaning those whose disorder has failed to respond to conventional therapies. In July 2023, its label was expanded to include children, ages 6-17, with refractory gMG who were positive for anti-AchR antibodies.

In Japan, Soliris also is approved for anti-AChR positive adults and children whose symptoms are not effectively controlled with high-dose intravenous (into-the-vein) immunoglobulin therapy (IVIG) or plasmapheresis, also called plasma exchange.

Who should not take Soliris?

Soliris is not recommended for patients who have serious and unresolved infections with Neisseria meningitidis bacteria, which can cause a serious condition called meningococcal disease.

It also should not be used in people who are not vaccinated against this bacterial species, except if the risks of postponing treatment outweigh the potential risks of developing a meningococcal infection.

The prescribing label for Soliris has a boxed warning for serious, life-threatening meningococcal infections, as these have occurred in patients treated with the medication. Patients should be carefully monitored for signs of infection.

How is Soliris administered in MG?

In the U.S., Soliris is administered via an intravenous, or into-the-vein infusion at a recommended maintenance dose of 1,200 mg, given every two weeks.

However, for those initiating treatment, there is an initial loading period of five doses: the first four involve weekly 900 mg infusions of the medication, and the fifth delivers the recommended 1,200 mg maintenance dose one week later. From that point on, patients receive the recommended 1,200 mg maintenance dose every two weeks.

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 also should be monitored for at least one hour for signs or symptoms of infusion reactions.

In Europe, where Soliris is also approved for younger patients, dosing recommendations are similar for adults and children weighing 40 kg (about 88 pounds) or more. However, loading and maintenance doses, as well as dosing frequency, must be adjusted in patients weighing less than 40 kg.

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 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 remission.

Compared with the year before entering REGAIN, patients also experienced 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 that Soliris led to sustained improvements in muscle strength and was effective across ethnicities. Treatment with Soliris also did not increase the patients’ 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 previously been treated with, and failed to respond to, another medication called rituximab. That therapy is being investigated for use 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 did not 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, ages 6 to 17, with AchR-positive refractory gMG. Children 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 that 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 week one and were sustained through week 26.
The therapy’s safety profile in children was consistent with its profile in older 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. Other common side effects that occurred more frequently in Soliris-treated patients than those on a placebo included:

• abdominal pain
• swelling in the arms and legs
• infections with the herpes simplex virus
• bruises.

Infections

Soliris carries a boxed warning for serious meningococcal infections, which can rapidly become life-threatening or fatal if not detected and treated early.

People starting on this medication should be vaccinated according to current guidelines and should receive a meningococcal vaccine at least two weeks before starting treatment. There is an exception relative to the vaccine if the risks of delaying treatment outweigh the potential risks of meningococcal infections.

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 immediately evaluated if an infection is suspected. Because Soliris dampens immune responses, caution is recommended when administering the therapy to people with any infection.

Infusion-related reactions

Soliris can cause infusion-related reactions, which can include allergic reactions, such as anaphylaxis. Yet, no patients have discontinued the medication in clinical trials due to infusion reactions. 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.

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