IgG1 antibody demonstrates efficacy, tolerability for patients with myasthenia gravis

Efgartigimod, a human IgG1 antibody designed to decrease pathogenic IgG autoantibody levels, demonstrated efficacy and tolerability among patients with generalized myasthenia gravis, according to findings published in The Lancet Neurology.

“Although there are treatment options available to patients with generalized myasthenia gravis, they are frequently burdensome, have substantial side-effects, do not alleviate symptoms, or are reserved for refractory patients,” the researchers wrote. “ADAPT was the largest clinical trial in patients with generalized myasthenia gravis and the only one to include patients regardless of their autoantibody status.”

James F. Howard Jr., MD, distinguished professor of neuromuscular disease and professor of neurology and medicine at the University of North Carolina at Chapel Hill, and colleagues conducted the randomized, double-blind, placebo-controlled, phase 3 ADAPT trial across 56 neuromuscular academic and community centers in 15 countries in North America, Europe and Japan. The trial enrolled patients aged at least 18 years with generalized myasthenia gravis who had a Myasthenia Gravis Activities of Daily Living score of at least 5 and were receiving a stable dose of at least one treatment for the disease.

Using interactive response technology, the researchers randomly assigned patients 1:1 to efgartigimod (ARGX-113, Argenx) 10 mg/kg or matching placebo, given as four infusions per cycle with one infusion per week. They repeated this process as necessary based on clinical response but did so at least 8 weeks after the start of the last cycle.

The primary outcome was the number of acetylcholine receptor antibody-positive patients who responded according to the Myasthenia Gravis Activities of Daily Living scale, where an improvement in the scale of at least two points was maintained for 4 or more weeks in the first treatment cycle. The researchers conducted the primary analysis in the modified intention-to-treat population among all acetylcholine receptor antibody-positive patients with a valid Myasthenia Gravis Activities of Daily Living evaluation from baseline and at least one Myasthenia Gravis Activities of Daily Living evaluation after baseline. The safety analysis included all patients who were randomly assigned and received at least one dose or partial dose of either efgartigimod or placebo.

Howard and colleagues enrolled, randomly assigned and treated 167 patients between Sept. 5, 2018, and Nov. 26, 2019, including 84 patients in the efgartigimod group and 83 patients in the placebo group. The study included primarily patients who were acetylcholine receptor antibody positive (n = 129; 77%).

Of these acetylcholine receptor antibody-positive patients, more of them enrolled in the efgartigimod group achieved a response according to the Myasthenia Gravis Activities of Daily Living assessment (n = 44 of 65; 68%) during the first cycle than in the placebo group (n = 19 of 64; 30%), according to the study results. This translated to an OR of 4.95 (95% CI, 2.21-11.53).

Treatment-emergent adverse events occurred in 65 patients (77%) in the efgartigimod group and in 70 patients (84%) in the placebo group. The most common of these events included headache (efgartigimod, n = 24 [29%] vs. placebo, n = 23 [28%]) and nasopharyngitis (efgartigimod, n = 10 [12%] vs. placebo, n = 15 [18%]). Serious adverse events developed in four patients in the efgartigimod group (5%) and in seven patients (8%) in the placebo group. Three patients in each group (4%) stopped treatment during the study. The researchers reported no deaths.

Howard and colleagues cited the follow-up duration as one of the study’s limitations, noting that it will be addressed during the ongoing, open-label extension study. However, they also noted that the retreatment criteria, which required that patients’ Myasthenia Gravis Activities of Daily Living score return to a less than 2-point decrease from baseline, “was a rigorous ADAPT study criterion and the usefulness in the real world will be established in clinical practice,” according to the study results.

“The results of the phase 3 ADAPT trial suggest that the novel mechanism of selective IgG reduction through blocking of [neonatal Fc receptor] with efgartigimod is an effective and well tolerated treatment for patients with generalized myasthenia gravis,” Howard and colleagues wrote.