Soliris Effective and Safe in Real-world Use, Japanese Study Reports

Soliris (eculizumab) was found in a real-world setting to safely and effectively treat adults with generalized myasthenia gravis (gMG) who had stopped responding to other treatments, according to a post-marketing surveillance study in Japan.

The study “Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: interim analysis of post-marketing surveillance,” was published in Therapeutic Advances in Neurological Disorders.

Soliris was approved in Japan in 2017  to treat people with gMG who have self-reactive antibodies against acetylcholine receptors (AChRs), the most common cause of MG, and whose symptoms are difficult to control using other immunosuppressive therapies (refractory disease). It is approved in the U.S. and EU for this same patient group.

The medication, developed and marketed by Alexion, works by blocking the activity of the C5 protein, which is one of more than 30 proteins belonging to the complement system — a part of the immune system thought to be involved in the autoimmune responses seen in MG patients.

Soliris’ approvals were supported by data from the international Phase 3 REGAIN trial (NCT01997229) and its open-label extension study (NCT02301624). Trial data showed the therapy to be safe and effective at improving muscle strength and quality of life in gMG patients who had ceased responding to other treatments.

As the number of Japanese patients in these trials was limited, the country’s regulatory agency requested a post-marketing surveillance study to evaluate Soliris’ clinical use by people with refractory gMG in Japan.

Researchers now report findings from an interim analysis of this study, covering 40 Japanese adults (62.5% women) treated with Soliris between 2017 and 2019.

All 40 were included in safety analyses, but six who were enrolled in REGAIN’s open-label extension study were excluded from evaluations of treatment effectiveness.

All had tested positive for AChR antibodies, had previously used corticosteroids and/or immunosuppressants, and were vaccinated against Neisseria meningitidis — bacteria that can cause meningitis — before starting Soliris, fulfilling the requirements of the therapy’s prescribing information.

Most, 92.5%, had also been treated with intravenous antibodies (intravenous immunoglobulin, or IVIG) and/or plasmapheresis. Of note, plasmapheresis is a process by which the blood is “cleaned” by removing patients’ plasma — the liquid portion of blood — containing harmful self-reactive antibodies and replacing it with that of a healthy donor.

A total of 15 patients (37.5%) were diagnosed with a thymoma, a tumor in the thymus gland, at some point.

Treatment with Soliris was maintained for a mean of 6.6 months (28.8 weeks). At the time of the analysis (26 weeks), 80% of these patients were still on Soliris; eight (20%) discontinued treatment due to adverse events or inadequate response. Patients with a history of thymoma were more likely to stop using Soliris than were those without one (33.3% vs. 12%).

Adverse events were reported in 16 patients, and considered related to Soliris’ use in seven people, all over age 65 and with a history of MG flares, including myasthenic crisis. Side effects related to treatment included headache (the most frequent), nasopharyngitis (the common cold), influenza-like illness, intestinal perforation, and vomiting.

Side effects were considered serious in four patients, and included in three of them the common cold, influenza-like illness, and intestinal perforation. A fourth person had an abnormal heartbeat and heart attack. All adverse events were more common among patients who did not have a history of thymoma.

Two deaths were reported during the study. One patient with a history of diabetes and hypertension died of heart attack; a causal link to Soliris remained unclear. The other died of an MG crisis within 45 days after stopping treatment.

Soliris’ use resulted in improvements, as indicated by the lower MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores relative to those recorded at the study’s start. MG-ADL is a patient-reported scale commonly used to address symptom severity in MG, and QMG is a reliable physician-reported  scale often used in clinical studies.

Over 75% of patients reported an improvement of more than three points in the MG-ADL, and more than 50% of more than five points in the QMG, both measured after 26 weeks of treatment and relative to scores at the study’s start. While no differences were seen in patients with or without a history of thymoma on MG-ADL scores, QMG scores tended to be better in those with a tumor history.

Six of the 34 patients in these efficacy analyses saw a worsening of their condition during follow-up.

In agreement with trial findings, treatment with Soliris was linked with a lesser need for immunosuppressive treatment.  Fewer patients were using more than one intravenous immunosuppressive therapy after starting on Solaris, the researchers reported, a reduction from 59% in the six months prior to treatment start to 15% six months after its initiation.

“In a real-world setting, eculizumab was effective and well tolerated for the treatment of AChR+ gMG in adult Japanese patients,” the researchers wrote.

“These findings are consistent with the efficacy and safety results from the global phase III REGAIN study of eculizumab,” they concluded.