Efgartigimod Aims to Become First Therapy for Seronegative Generalized Myasthenia Gravis Following Positive Phase 3 Data

James F. Howard, MD

Newly announced topline data from the phase 3 ADAPT SERON study (NCT06298552) showed that intravenous (IV) efgartigimod (Vyvgart; argenx) met its primary end point, demonstrating significant and clinically meaningful impacts on patients with seronegative myasthenia gravis (gMG), a patient population with no FDA approved treatments. Based on these findings, the company is planning to submit a supplemental biologics license application (sBLA) to expand its indication in seronegative gMG across 3 subtypes: muscle-antibody specific kinase (MuSK), LRP4+, and triple seronegative.¹

ADAPT-SERON, a randomized, double-blind, placebo-controlled study featured 119 patients across numerous continents who were randomized to receive 4 once-weekly IV infusions of efgartigimod or placebo, followed by a 5-week follow-up and primary analysis. Overall, the treatment with efgartigimod let to statistically significant (P = .0068) impacts on Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, the primary end point, after 29 days in Part A of the study.

To date, no FDA-approved therapy is specific to completely seronegative gMG, as well as no approved treatments for those with anti-LRP4 antibodies or triple seronegative patients. Efgartigimod, an FcRn inhibitor, was originally approved in 2021 in an IV form as a treatment for seropositive patients with gMG who are anti-acetylcholine receptor antibody negative (AChR).² Rozanlixizumab remains the only approved agent that extends beyond AChR to MuSK-positive gMG.

"The results of the ADAPT SERON study, the largest study to date of AChR-Ab seronegative gMG, confirm that VYVGART now has the potential to be a targeted, effective, safe, and necessary treatment for patients living with gMG, regardless of autoantibody status," principal investigator James F. Howard, MD, professor of neurology, The University of North Carolina at Chapel Hill School of Medicine, said in a statement.

He added, "Paired with our existing knowledge, these data demonstrate that pathogenic IgGs are underlying drivers of gMG across patient subtypes. This is a critical advancement in the management of this debilitating and unpredictable disease for patients with limited treatment options."

Argenx is planning to shared more detailed results from ADAPT SERON at an upcoming medical meeting. ADAPT SERON included a double-blind Part A, followed by an open-label extension, where patients received 2 fixed cycles of 4 once-weekly efgartigimod infusions. From cycle 3 onward, additional cycles could be started at least 1 week after the last administration of the previous cycle, based on clinical status. Currently, ADAPT SERON remains the only global phase 3 study to show clinically meaningful improvements in disease activity across all 3 subtypes: MuSK+, LRP4+, and triple seronegative.

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According to clinicaltrials.gov, the trial’s extension is expected to last until 2027. Patients with any known autoimmune disease or condition that would interfere with an accurate assessment of clinical symptoms of gMG were excluded. In addition, the study barred those with a clinically significant active infection, known hypersensitivity to the study drug, recent thymectomy, or received a live/live-attenuated vaccine within 4 weeks before screening.

Luc Truyen, MD, PhD

"The ADAPT SERON study represents our longstanding commitment to the MG community and our ambition to help all MG patients address this debilitating condition and reach as many MG patients as we can," Luc Truyen, MD, PhD, chief medical officer at argenx, said in a statement.¹ "The positive outcome of the ADAPT SERON study clearly shows VYVGART’s ability to provide meaningful benefit across all AChR-ab seronegative gMG subtypes."

Over the years, diagnosing seronegative gMG has been difficult due to the absence of reliable antibody markers and overlapping clinical features, while treatment has been hampered by the lack of targeted, approved therapies and inconsistent responses to conventional immunosuppression. Clinicians have observed less predictable treatment responses with seronegative patients, making management more individualized. Notably, many trials in the past have excluded seronegative patients, limited data and slowing progress toward tailored treatments.

REFERENCE
1. argenx Announces Positive Topline Results from ADAPT SERON Study of VYVGART in Patients with AChR-Ab Seronegative gMG. Argenx. August 25, 2025. Accessed August 25, 2025. https://argenx.com/news/2024/argenx-announces-positive-topline-results-from-adapt-seron-study
2. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed August 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis