ADAPT SERON Trial Shows Positive Results for Seronegative gMG

NeurologyLive^® published an earlier version of this article.

Intravenous (IV) efgartigimod (Vyvgart; argenx) had a significant and clinically meaningful impact on patients with seronegative generalized myasthenia gravis (gMG), a patient population for whom there are no FDA-approved treatments, according to newly announced topline data from the phase 3 ADAPT SERON study (NCT06298552). Based on these findings, the company is planning to submit a supplemental biologics license application to expand its indication in seronegative gMG across 3 subtypes: muscle-specific kinase antibody–positive (MuSK+), lipoprotein receptor–related protein 4–positive (LRP4+), and triple seronegative.¹

ADAPT SERON, a randomized, double-blind, placebo-controlled study featured a global population of 119 patients who were randomized to receive 4 once-weekly IV infusions of efgartigimod or placebo, followed by a 5-week follow-up and primary analysis.² Overall, treatment with efgartigimod led to statistically significant (P = .0068) impacts on Myasthenia Gravis Activities of Daily Living total score, the primary end point, after 29 days in part A of the study.

To date, no FDA-approved therapy has an indication specific to seronegative gMG, and there are no approved treatments for those with anti-LRP4 antibodies or who have triple-seronegative disease. Efgartigimod, a neonatal Fc receptor blocker, was originally approved in 2021 for IV administration for seropositive patients with gMG who also are anti–acetylcholine receptor antibody negative (AChR Ab–).³

"The results of the ADAPT SERON study, the largest study to date of AChR-Ab seronegative gMG, confirm that [efgartigimod] now has the potential to be a targeted, effective, safe, and necessary treatment for patients living with gMG, regardless of autoantibody status," said principal investigator James F. Howard, MD, professor of neurology, The University of North Carolina at Chapel Hill School of Medicine, in a statement. “Paired with our existing knowledge, these data demonstrate that pathogenic IgGs [immunoglobulin G] 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."

Diagnosing seronegative gMG has been difficult, experts note, due to the absence of reliable antibody markers and overlapping clinical features, and treatment has been hampered by the lack of targeted agents. | Image Credit: © lexiconimages-stock.adobe.com

Argenx is planning to share more detailed results from ADAPT SERON at an upcoming medical meeting. The study 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 the 3 subtypes: MuSK+, LRP4+, and triple seronegative.

The trial’s expected completion date is July of 2027.² Patients with any known autoimmune disease or condition that would interfere with accurate assessment of clinical symptoms of gMG and those with a clinically significant active infection, known hypersensitivity to the study drug, recent thymectomy, or who received a live or live-attenuated vaccine within 4 weeks of screening are excluded from participation.

"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," said Luc Truyen, MD, PhD, chief medical officer, argenx, in a statement. "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, and 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 among patients with seronegative disease, making management more individualized. Notably, many trials in the past have excluded these patients, thereby limiting data and slowing progress toward tailored treatments.

References

1. argenx announces positive topline results from ADAPT SERON study of Vyvgart in Patients with AChR-Ab seronegative gMG. News release. Argenx. August 25, 2025. Accessed August 28, 2025. https://argenx.com/news/2024/argenx-announces-positive-topline-results-from-adapt-seron-study
2. A phase 3 study to evaluate the efficacy and safety of efgartigimod IV in patients with acetylcholine receptor binding antibody seronegative generalized myasthenia gravis (ADAPT SERON). ClinicalTrials.gov. Updated June 13, 2025. Accessed August 28, 2025. https://www.clinicaltrials.gov/study/NCT06298552
3. FDA approves new treatment for myasthenia gravis. News release. FDA. December 17, 2021. Accessed August 28, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis