Soliris May Be Safe, Effective for Rituximab-refractory gMG

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Soliris (eculizumab) appears to be safe and effective for patients with hard-to-treat generalized myasthenia gravis (gMG) who have acetylcholine receptor (AChR) antibodies, a study has found.

Its benefits were extended to a particular group of patients from the Phase 3 REGAIN clinical trial and its extension study who were treated previously with — but did not respond, or were refractory to — rituximab.

The findings suggest that Soliris may work for patients with gMG “irrespective of their disease features and treatment history, including patients with refractory disease who have received rituximab treatment previously,” the researchers wrote.

The study, “Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study,” was published in the journal Muscle & Nerve.

About 10–15% of patients with gMG fail to respond to conventional treatment with immunosuppressants and are considered refractory cases.

Treatment guidelines recommend rituximab — a medication that works by lowering the numbers of B-cells, a type of immune cell that produces antibodies — as an option for patients with refractory gMG who stop responding, or are intolerant to other medications. However, the disease also may become refractory to rituximab.

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“Therefore, patients with a history of rituximab use and persistent symptoms represent a population with [an] unmet treatment need,” the researchers wrote.

Most patients with gMG have AChR antibodies that can activate the complement system, which is a cascade of events that help the body’s immune system clear germs and damaged cells from the body.

Alexion’s Soliris — a medication that works by binding to C5, a specific component of the complement system, making the cascade come to a stop — may provide an alternative treatment approach for those patients.

Its efficacy and safety have been assessed in REGAIN, a six-month, placebo-controlled Phase 3 trial (NCT01997229), and its four-year, open-label extension (OLE) study (NCT02301624). In these trials, Soliris improved muscle strength and patients’ ability to carry out daily activities living, while reducing the use of immunosuppressants.

While most patients benefitted from Soliris within the first three months of treatment, others had to wait longer to see their symptoms ease.

Now, researchers have reported findings from a new analysis of data from REGAIN and its OLE to evaluate the efficacy and safety of Soliris in patients with refractory gMG who have AChR antibodies and have been treated previously with rituximab.

Of the 125 patients who were treated in REGAIN, 14 had received rituximab: seven of those were in the Soliris arm of the study, and the other seven were in the placebo arm. All but one in the placebo group continued to the OLE.

Compared with rituximab-naïve patients, those who had received the therapy previously were younger at the time of diagnosis (27.6 vs. 39.4 years) and had a longer mean disease duration (13.9 vs. 9.0 years).

Patients previously treated with rituximab also were more likely to have received intravenous immunoglobulin (100% vs. 76.6%) or had undergone a thymectomy (85.7% vs. 50.5%) than those who had never been treated with rituximab. They also were more likely to have tried four or more different immunosuppressants (57.1% vs. 16.2%).

In both groups, patients experienced an improvement in activities of daily living (ADL) after 130 weeks (about 2.5 years) of starting treatment with Soliris. This was measured using the MG-ADL score, which dropped by a mean of 4.6 points in rituximab-naïve patients and by a mean of 4.4 points in those who had received the medication previously.

In both groups, most patients (65.0–66.7%) achieved a MG Foundation of America Post-intervention Status of “minimal manifestations,” meaning they had no functionally limiting symptoms, despite some muscle weakness.

“This analysis has shown that patients who were treated with rituximab previously, and who may therefore represent a patient group with an unmet treatment need, also experienced rapid and long-term clinical improvements with eculizumab, similar to those seen in the general study population,” the researchers concluded.

The safety profile of Soliris was similar between the groups. Among the four patients who had received rituximab in the year prior to starting Soliris, there were three reports of infection. No side effects were reported in the placebo arm.