Efgartigimod, an injectable human IgG1 antibody Fc fragment that targets the neonatal Fc receptor (FcRn), lessens disease severity in patients with generalized myasthenia gravis (gMG) who lack detectable anti-acetylcholine receptor (AChR) antibodies, according to results of the phase 3 ADAPT SERON trial presented at the American Association of Neuromuscular & Electrodiagnostic Medicine 2026 Annual Meeting.
Patients treated with efgartigimod had a significantly greater reduction in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at 4 weeks compared with those treated with placebo (least-squares [LS] mean -3.35 vs -1.90 points; P=0.007), with generally consistent effects across subgroups, reported James Howard Jr, MD, a neurologist at the University of North Carolina at Chapel Hill.
“The primary endpoint was met—statistically significant improvement at week 4 following a single cycle versus placebo,” he said, adding that the study “demonstrates that pathogenic antibodies are a key underlying driver” of gMG, irrespective of autoantibody status.
Dr. Howard said that many patients with gMG have unmet needs, particularly those lacking anti-AChR antibodies: “It’s a population that desperately needs therapy and hence this trial.”
ADAPT SERON included 119 patients with gMG without anti-AChR antibodies and a baseline MG-ADL score ≥5. Mean patient age was about 51 years, and 76% were women. The population included anti-MuSK-Ab+, anti-LRP4-Ab+, and triple-seronegative patients.
In Part A, patients were randomized to four weekly doses of efgartigimod 10 mg/kg or placebo. During Part B, an open-label phase, patients received additional cycles of treatment. At the time of the current analysis, 60% of patients had completed cycle 9.
Efgartigimod-treated patients were more likely to have a history of prior thymectomy (24.1% vs 6.6%), to be receiving a nonsteroidal immunosuppressive therapy (53.4% vs 36.1%), and to be in the anti-LRP4-Ab+ subgroup (10.3% vs 0) than those in the placebo group.
The reduction in MG-ADL total score at week 4 was significantly greater with efgartigimod versus placebo in the overall cohort (LS mean difference -1.46) and in the anti-MuSK-Ab+ subgroup (LS mean difference -2.35; P=0.01). There was a similar trend in the triple-seronegative subgroup but it was not significant (LS mean difference -0.98; P=0.15). Small patient numbers precluded reliable estimates in the anti-LRP4-Ab+ subgroup.
The improvements in MG-ADL score with active treatment were sustained through 52 weeks during the open-label phase, both in the overall cohort and within each subgroup.
“Beyond the initial cycle, additional improvement is seen over time with subsequent cycles,” Dr. Howard said.
A similar pattern was observed in an analysis looking at the proportion of patients who achieved at least 2-, 3-, and 4-point improvements in MG-ADL total score after each subsequent cycle and in an analysis of the achievement of minimal symptom expression (MG-ADL total score 0 or 1).
“More treatment gives you an improved response, and I think that becomes important as we determine is this a go or no go for my patient,” Dr. Howard said. “With the AChR population, we said two, three cycles [and] if they don’t respond, one might abandon it. I’m not sure we can apply the same metric here.”
In terms of safety, efgartigimod was well tolerated, with rates of adverse events similar to what has been seen in prior clinical and real-world studies, he said.
