Efficacy and Safety of Efgartigimod in Anti-Acetylcholine Receptor Antibody–Negative Generalized Myasthenia Gravis: Initial Results of ADAPT SERON

Topic:

Clinical Trials

Poster Number: 222 M

Author(s):

Sharon Reizner, PharmD, argenx, James F. Howard Jr., MD, University of North Carolina, Tuan Vu, MD, University of South Florida, Chongbo Zhao, Department of Neurology, Huashan Hospital, Fudan University, Sushan Luo, Department of Neurology, Huashan Hospital, Fudan University, Sarah Hoffmann, Department of Neurology and Neuroscience Clinical Research Center, Charité – Universitätsmedizin Ber, Kristl G. Claeys, Department of Neurology, University Hospitals Leuven, Belgium, Rosa H. Jimenez, argenx, Ghent, Ineke Seghers, argenx, Ghent, Delphine Masschaele, argenx, Ghent, Wan-Yi Huang, argenx, Ghent, Łukasz Rzepiński, 10th Military Research Hospital and Polyclinic; Faculty of Medicine, University of Science and Tech, Elisabeth Chroni, Department of Neurology, University Hospital of Patras, Ali Alshehri, Department of Neurology, King Faisal Specialist Hospital and Research Centre, Ari Breiner, Division of Neurology, The Ottawa Hospital/The University of Ottawa

Background
Approximately 15%-20% of patients with generalized myasthenia gravis (gMG) are classified as anti-acetylcholine receptor antibody (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.

Objectives
To evaluate the efficacy and safety of efgartigimod IV in adults with AChR-Ab seronegative gMG in a Phase 3 trial (ADAPT SERON; NCT06298552).

Methods
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).

Results
Topline results included 119 participants (n=40, muscle-specific kinase antibody seropositive [MuSK-Ab+]; n=6, low-density lipoprotein receptor-related protein 4 antibody seropositive [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=0.007) 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. Further 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.

Conclusions
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.