Soliris Shows Sustained Efficacy and Safety for gMG in Extension Study
Treatment with Soliris (eculizumab) provided adults with generalized myasthenia gravis (gMG) clinically meaningful improvements through three years in daily living, muscle strength, functional ability and quality of life, according to early data from an extension study. Lower rates of MG exacerbations and hospitalizations were also observed.
The study, “Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis,” appeared in the journal Muscle & Nerve.
These results indicate that Soliris leads to sustained benefits, as the REGAIN Phase 3 trial (NCT01997229) in the same patients had shown similar improvements. An earlier analysis of this extension study had already demonstrated the continuation of therapeutic benefits.
The Alexion-sponsored open-label extension study of REGAIN (NCT02301624) intended to assess Soliris’ long-term safety and efficacy in 117 patients with anti-acetylcholine receptor antibody-positive gMG not responding to two or more immunosuppressive therapies. Treatment with Soliris lasted a maximum of four years.
During the 4-week blinded induction phase, the patients previously on Soliris received this therapy (1,200 mg) on day 1 and week 2, and placebo at weeks 1 and 3. In turn, those previously on placebo received 900 mg Soliris and placebo on day 1 and at weeks 1, 2 and 3. Then, in the maintenance phase, all participants received 1,200 mg Soliris every two weeks.
Thirty-eight patients required Neisseria meningitides revaccination to lessen the risk of meningococcal infection associated with Soliris’ inhibition of the complement system — a set of more than 20 blood proteins that are part of the body’s immune defenses. The participants were also receiving a stable regimen of other MG therapies, including the immunosuppressants azathioprine, cyclophosphamide, cyclosporine, and methotrexate.
Activities of daily living, muscle strength, functional ability and quality of life were assessed with the MG-ADL scale, the Quantitative MG scale (QMG), the MG Composite scale (MGC) and the 15-item MG Quality of Life questionnaire (MG-QOL15), respectively.
To evaluate Soliris’ safety, the team analyzed adverse events (AEs), study discontinuations due to AEs, exacerbations, hospital admissions, and rescue therapy administration.
As of the cutoff date for the analysis (Dec. 31, 2017), 73% of patients were still participating in the study. Five had completed it, while 27 had discontinued. Six patients discontinued treatment due to one or more adverse events, 12 withdrew consent, and three died. One patient stopped the therapy for factors including ongoing comorbidities, perceived lack of clinical benefit, and problems with clinic attendance.
Median duration of treatment with Soliris was 22.7 months, ranging from 1 day to 37.3 months. The safety profile was consistent with REGAIN. The most common AEs were headache (37.6%) and nasopharyngitis (31.6%). The most common serious AE was MG worsening, in 12.8% of patients. Twenty-two patients (18.8%) experienced an infectious event regarded as of “special interest,” including five cases of sepsis.
No cases of meningococcal infection were reported within the analysis period. The case that occurred after the cutoff data was resolved with antibiotics.
Twenty-nine patients experienced 59 MG exacerbations, including MG crises, substantial symptom worsening and health at risk without rescue therapy. This represented a 75.2% reduction compared to the year before starting REGAIN. It was significantly lower than in patients on placebo during REGAIN.
MG-related hospitalizations were also lower with Soliris than in the year prior to REGAIN. Both the hospitalizations and the use of rescue therapy were reduced with Soliris compared to placebo.
The data further revealed that the improvements in activities of daily living, muscle strength, functional ability and quality of life found in REGAIN were maintained through a maximum treatment duration of three years. Patients on placebo during REGAIN experienced sustained (over 30 months) benefits as early as the first visit in the extension study, similar to those of patients on Soliris during REGAIN.
At the last assessment, 55.2% of patients had a clinically meaningful response in activities of daily living, which increased to 71.6% if regardless of rescue therapy. Also, 39.7% of patients experienced a clinically meaningful response in muscle strength, 48.3% if regardless of rescue treatment.
As reported by the investigators, 74.1% had clinical improvements compared to the start of REGAIN. Most (56%) achieved minimal MG manifestations or pharmacological remission.
“In conclusion, results of this interim analysis confirm the rapid and robust response to eculizumab (Solirs) observed during REGAIN and support the long-term clinical effectiveness and safety of eculizumab in patients with AChR+ refractory gMG,” the scientists stated.
Of note, three of the study’s authors are or were full-time employees at Alexion. Ten were paid consultants for the company, two were site investigators, and two others received research support and/or honoraria from Alexion.