Soliris (eculizumab), developed by Alexion Pharmaceuticals, is approved in the U.S., Europe, and Japan to treat adults with generalized myasthenia gravis (gMG) who are positive for antibodies against the acetylcholine receptor — the most common type of MG-causing antibody.
Soliris is also approved by the U.S. Food and Drug Administration (FDA) for the treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome (aHUS), and neuromyelitis optica spectrum disorder (NMOSD).
How does Soliris work?
MG is an autoimmune disease in which a person’s immune system erroneously attacks the connections between nerves and muscles, impairing nerve-muscle communication. This immune attack is driven by self-reactive antibodies; most commonly, these antibodies (referred to as anti-AChR antibodies) target the acetylcholine receptor, a protein receptor that plays a key role in nerve-muscle communication and muscle contraction.
Soliris is designed to block part of the immune system called the complement cascade. This cascade 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 cascade becomes activated. This is believed to contribute to the damaging immune response seen in MG.
Soliris specifically binds to a complement protein called C5, preventing its cleavage into other complement components and ultimately blocking complement activation.
Soliris in clinical trials
Regulatory approvals of Soliris were supported by data from a Phase 3 trial called REGAIN (NCT01997229). The Alexion-sponsored trial, which ended in June 2016, was a double-blind, placebo-controlled global study that evaluated the safety and efficacy of Soliris in 125 anti-AChR-positive gMG patients who failed to respond to immunosuppressive treatments (refractory disease). Participants were randomized to receive either Soliris or a placebo for 26 weeks (around half a year).
The main goal of REGAIN was to assess the treatment’s effect on changes in the myasthenia gravis activities of daily living (MG-ADL) score, which measures the ease of doing daily activities.
Although Soliris-treated participants tended to have better MG-ADL scores at the trial’s conclusion, the difference between groups did not reach statistical significance, according to top-line results announced in 2016. However, Soliris significantly outperformed placebo in scores on the Quantitative Myasthenia Gravis (QMG), a measure of disease severity.
Most participants in REGAIN (117 out of 125) elected to enroll in its open-label extension study (NCT02301624), where all were treated with Soliris and monitored for long-term safety and efficacy.
Data from the extension study generally showed the benefits of Soliris seen in the original trial were sustained with prolonged treatment. A 2019 analysis indicated that — after a median treatment duration of 22.7 months — nearly three out of four participants experienced clinical improvements compared with the start of REGAIN, and over half had minimal manifestations of the disease. Soliris also reduced rates of MG exacerbations (episodes of sudden symptom worsening) and hospitalizations.
Other analyses of data from the two studies showed that Soliris led to sustained improvements in muscle strength, was effective across ethnicities, did not increase the risk of infection, and lowered the need for other immune-suppressing medicines. The treatment also was shown to be effective in participants who had previously been treated with, and failed to respond to, another medication called rituximab.
A post-hoc analysis done after the trials were completed indicated that most participants responded to Soliris within three months of starting treatment; however, for more than 15% of participants in the analysis, a response did not become evident until later times.
Soliris is administered via an infusion directly into the bloodstream. The dosing regimen for gMG is 900 mg weekly for the first four weeks, followed by 1,200 mg for the fifth dose a week later, and then 1,200 mg every other week thereafter.
The most common side effects associated with Soliris in studies of gMG is musculoskeletal (muscle-and-skeleton) pain. Other side effects commonly associated with the medication in other indications include headache, the common cold, nausea, and diarrhea.
Soliris caries a warning for serious meningococcal infections, a bacterial infection that can be fatal. Patients should be vaccinated against meningococcal disease at least two weeks before starting on Soliris. Those with current infections should not be started on Soliris, and treatment should be discontinued in individuals who develop a meningococcal infection. Caution is recommended if giving Soliris to people with any other kind of systemic infection.
Last updated: Jan. 25, 2022, by Marisa Wexler MS
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