To evaluate the efficacy and safety of efgartigimod IV in adults with anti-acetylcholine receptor antibody (AChR-Ab) seronegative generalized myasthenia gravis (gMG) in a Phase 3 trial (ADAPT SERON).

Approximately 15%-20% of patients with gMG are classified as AChR-Ab seronegative. There is an unmet need for approved treatments for the AChR-Ab seronegative gMG population. Efgartigimod is a human immunoglobulin G1 (IgG1) antibody Fc fragment that reduces IgG levels (including pathogenic autoantibodies) via neonatal Fc receptor blockade.

Diagnosis of gMG was confirmed by an MG diagnostic adjudication committee. In the double-blinded, placebo-controlled Part A, adult participants were randomized 1:1 to receive 4 once-weekly infusions of 10 mg/kg efgartigimod IV or placebo followed by a 5-week follow-up period. Part B included an open-label extension (≤2 years).

Topline results included 119 participants (n=40, MuSK-Ab+; n=6, LRP4-Ab+; n=73, triple seronegative), 58 received efgartigimod IV, and 61 received placebo. The change in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score from baseline to week 4 (primary endpoint) was significantly (P=0.0068) different between efgartigimod IV and placebo groups (overall population), with least squares mean difference (90% CI) of −3.35 (−3.98 to −2.72) and −1.90 (−2.51 to −1.28) in each group, respectively. Incremental improvements in MG-ADL total scores were observed during Part B over subsequent treatment cycles across all three subgroups. Efgartigimod IV was well tolerated, with no new safety signals observed.

Efgartigimod IV demonstrated statistically significant improvement in MG-ADL total score compared with placebo (primary endpoint), with a clinically meaningful change from baseline, and was well tolerated in participants with AChR-Ab seronegative gMG.