#AANAM — Soliris May Help MG Patients Lower Immunosuppressive Therapy Use, Phase 3 Data Show

A significant proportion of patients with generalized myasthenia gravis (MG) treated with Alexion’s Soliris (eculizumab) were able to either stop or reduce their use of immunosuppressive therapy, according to interim results from a Phase 3 open-label extension study.

The study, “Changes in Concomitant Immunosuppressive Therapy Use During a Phase 3 Open-label Study of Eculizumab in Adults with Generalized Myasthenia Gravis: an Interim Analysis (P5.2-080),” was published in the journal Neurology and presented at the recent American Academy of Neurology annual meeting in Philadelphia.

Myasthenia gravis is a debilitating and progressive autoimmune disease that typically begins as weakness in the muscles that control the eyes and eyelids. Often, it progresses to a more severe and generalized form, known as generalized MG.

Patients with generalized MG often experience weakness of the head, neck, trunk, limb, and respiratory muscles. The disease is associated with several complications, exacerbations, and myasthenic crises that can be life-threatening and frequently require hospitalization.

While most symptoms associated with generalized MG can be managed using existing therapies, 10–15% of patients fail to respond or are intolerant toward multiple therapies. These patients continue to have significant muscle weakness and severe disease symptoms that limit daily functioning.

In patients with a subtype of MG known as anti-acetycholine receptor (AchR) antibody-positive MG, the body’s immune system produces antibodies against AchR, which plays a vital role in the communication between nerves and muscles.

The binding of these antibodies to AchR activates a component of the immune system known as the complement cascade, which leads to destruction of neuron-to-muscle signaling.

Soliris is the first and only inhibitor of the complement cascade that has been approved for the treatment of adults with generalized MG who are anti-AchR antibody-positive.

The safety and efficacy of Soliris for the treatment of gMG was established in a prior randomized, double-blind, placebo-controlled, multicenter Phase 3 trial called REGAIN (NCT01997229).

Data presented at AAN was from interim results of the open-label extension study (NCT02301624) of REGAIN, which included patients who participated in the initial trial and was intended to provide

long-term safety and efficacy information on Soliris in patients with refractory generalized MG.

MG patients are often on multiple therapies, including immunosuppressive therapy (IST). However, IST use is associated with significant side effects and a lower quality of life.

In this study, researchers specifically focused on changes made in the regimen of IST in patients being treated with Soliris.

The extension study enrolled 117 adults who had completed REGAIN. They received 1,200 mg of Soliris every two weeks after a four-week blinded induction phase.

Adjustments to parallel or concomitant MG therapies, including ISTs, were made at the investigators’ discretion. Concomitant medication use was recorded at all scheduled visits, as well as at unscheduled visits for MG crises.

At the start of the study, 115 of 117 patients (98.3%) were receiving at least one IST. Subsequently, 79 of these patients (67.5%) either stopped or decreased their dose of an IST on 439 occasions in total.

The most common reason for stopping or lowering the dose was due to patients experiencing fewer MG symptoms.

Conversely, 63 of the patients (53.8%) started or increased their dose of an IST on 189 occasions, most frequently because of MG symptom worsening.

“In eculizumab-treated adults with [generalized MG], a numerically larger proportion stopped or decreased the dose of a concomitant IST than started or increased the dose. MG symptom improvement and MG symptom worsening were the most common reasons for stopping/decreasing and starting/increasing IST, respectively,” the authors concluded.