Long-term Soliris Therapy Leads to Sustained Muscle Strength Improvement, Studies Show
Treatment with Soliris (eculizumab) led to rapid and sustained improvements in muscle strength and the ability to perform daily activities in people with refractory generalized myasthenia gravis (gMG) who have antibodies against acetylcholine receptors (AChRs), the Phase 3 REGAIN clinical trial and its extension study have shown.
Results of the study, “Consistent improvement with eculizumab across muscle groups in myasthenia gravis,” were published in the journal Annals of Clinical and Translational Neurology.
Soliris, developed by Alexion Pharmaceuticals, is approved to treat people with generalized MG who are positive for anti-AchR antibodies. Administered directly into the bloodstream, the therapy works by blocking the activity of a protein known as C5, which is one of more than 30 proteins belonging to the complement system — part of the immune system that induces the damaging autoimmune response seen in people with MG.
Soliris’ approval by the U.S. Food and Drug Administration in 2017 was based on positive data from the worldwide Phase 3 REGAIN clinical trial (NCT01997229) and its open-label extension study (NCT02301624).
In both studies, the ability to perform daily living activities was measured through the MG Activities of Daily Living (MG-ADL) scores and disease severity via the Quantitative MG (QMG) scale, which comprise four domains representing the muscles affected by gMG. Those include the eyes (ocular), lungs (respiratory), limbs (motor), and bulbar muscles, which are used for swallowing, speaking, and chewing.
Here, an international team, working with scientists at Alexion, conducted an analysis of REGAIN data and its extension study to determine whether Soliris was beneficial across all four muscle groups as measured by MG-ADL and QMG scores.
REGAIN was a six‐month trial in which participants received a 1,200 mg maintenance dose of Soliris or placebo every two weeks following a four-week induction period, for a total of 26 weeks. During the extension study, all participants received 1,200 mg Soliris every two weeks for up to four years. Median duration of treatment in the extension part was 2.7 years.
During REGAIN, 62 patients received Soliris and 63 received placebo. Of the 118 patients who joined the extension study, 56 had taken Soliris and 61 placebo. Almost three-quarters of participants (74.4%) completed this long-term study.
In patients who had received Soliris in the main trial, improvements in mean MG-ADL and QMG scores were sustained for 130 weeks (2.5 years) until the completion of the extension study.
People who switched from a placebo to Soliris experienced rapid improvements in mean MG-ADL and QMG scores from the start of Soliris treatment. Significant improvements in the extension study were seen as early as one week and were sustained for 130 weeks.
Among all participants, changes in MG-ADL scores correlated with those seen in the QMG scale from the start of REGAIN to completion of the extension study.
In an analysis of MG-ADL data alone, patients who stayed on Soliris experienced rapid improvements across all four MG-ADL domains during REGAIN, which were sustained or increased during the extension study. Peak improvements were seen by week 16 in all domains except the respiratory domain, which was observed after four weeks.
Patients who switched from a placebo showed sustained improvements in the ocular, bulbar, and limb domains as early as one week after starting on Soliris. The respiratory domain scores significantly improved by week four, and remained significant throughout.
Analysis of QMG data found that receiving Soliris since the main trial led to rapid and sustained improvements across all four domains. During REGAIN, peak improvements were seen by week 26 in the ocular and motor domains, week 20 in the bulbar domain, and week 12 in the respiratory domain. Except for the bulbar domain, peak improvements were sustained or increased during the extension study.
Participants switching from a placebo experienced significant improvements from the start of the extension study across all domains in one week, except for the bulbar domain, which improved by week 40. In the ocular and motor domains, improvements were significant for every week through 130 weeks. In the bulbar domain, patients improved until week 104, and in the respiratory domain until 16 weeks.
“In summary, the results reported here confirm previous REGAIN and interim OLE [open-label extension] data showing that eculizumab [Soliris] treatment results in rapid improvements in MG-ADL and QMG total scores that are sustained through at least 130 weeks in individuals with refractory AChR+ gMG,” the scientists wrote.
“Eculizumab treatment, therefore, rapidly induces clinical benefits across muscle groups, from both patient and physician perspectives, which are maintained in the long term in individuals with refractory AChR+ gMG,” they added.