sNDA Acceptance Positions Efgartigimod as Potential First Therapy for Seronegative Myasthenia Gravis

According to a company update, the FDA has accepted argenx’ supplemental new drug application (sNDA) for efgartigimod (Vyvgart), positioning itself as potentially the first treatment for adults with acetylcholine receptor antibody (AChR-Ab) seronegative generalized myasthenia gravis (gMG). The agency has granted a PDUFA target action date of May 10, 2026, for the decision.¹

Seronegative gMG, which affects around 15% of the total gMG population, has been typically treated using the same overall clinical playbook as antibody-positive gMG; however, there are no FDA-approved treatments specific to this subgroup. Efgartigimod, an engineered Fc fragment of human IgG1 designed to bind tightly to the neonatal Fc receptor, was originally approved for seropositive gMG in 2021 and had its indication expanded in 2024 to include the treatment of those with chronic inflammatory demyelinating polyneuropathy (CIDP).

Efgartigimod’s sNDA was based on data from the phase 3 ADAPT SERON study (NCT06298552), a randomized, double-blind, placebo-controlled trial that featured 119 patients followed over a 5-week treatment period. In the study, patients were randomly assigned to receive 4 once-weekly intravenous (IV) infusions of efgartigimod or placebo, with change in Myasthenia Gravis Activities of Daily Living (MG-ADL) as the primary end point, recorded at 29 days.

“Patients living with seronegative gMG continue to face limited treatment options and there remains a significant need to meaningfully improve their lives. The FDA’s acceptance of our sBLA with Priority Review status reflects the potential of VYVGART to address this need,” Luc Truyen, MD, PhD, chief medical officer at argenx, said in a statement.¹ “This development brings us closer to expanding the use of VYVGART in a broad spectrum of patients with myasthenia gravis. We look forward to continuing our dialogue with the FDA as they review our application.”

Overall, findings from ADAPT SERON showed that efgartigimod met its primary end point, with treated patients demonstrating statistically significant differences vs placebo (P = .0068) on MG-ADL total score. Patients on the approved medication showed a clinically meaningful 3.35-point improvement over the 29-day period, coupled with noticeable positive changes in breathing, eating, eyesight, and motor functions. Notably, investigators observed enhancements in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores, a secondary end point, across all patient subgroups, including MuSK+, LRP4+, and triple seronegative gMG.²

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ADAPT SERON featured a double-blind Part A followed by an open-label extension, in which patients received 2 fixed treatment cycles consisting of 4 once-weekly efgartigimod infusions. Beginning with cycle 3, additional cycles could be initiated at least 1 week after the final dose of the prior cycle, depending on a patient’s clinical status. To date, ADAPT SERON remains the only global phase 3 trial to demonstrate clinically meaningful improvements in disease activity across all 3 seronegative subtypes, including MuSK+, LRP4+, and triple seronegative gMG.

Coming into the study, patients were on a stable dose of at least 1 gMG medication prior to randomization, including acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressive drugs. The trial’s extension, expected to last until 2027, excludes patients with any known autoimmune disease or condition that would interfere with an accurate assessment of clinical symptoms of gMG. 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.

Efgartigimod’s original approval in gMG was based on data from the phase 3 ADAPT trial (NCT03669588), a 167-patient study that featured mostly patients who were AChR-Ab-positive (77%; n = 129). In ADAPT, a sustained response was observed in 88.6% of AChR-Ab+ patients who met the primary end point for at least 6 weeks, 56.8% for at least 8 weeks, and 34.1% for at least 12 weeks. Overall, the drug met its primary end point, outperforming placebo on MG-ADL scores (67.7% vs 29.7%; P <.0001) over the treatment period.³

REFERENCES
1. argenx Announces FDA Acceptance of Supplemental Biologics License Application with Priority Review for VYVGART in AChR-Ab Seronegative gMG. News release. Argenx. January 13, 2025. Accessed January 13, 2025. https://www.globenewswire.com/news-release/2026/01/13/3217457/0/en/argenx-Announces-FDA-Acceptance-of-Supplemental-Biologics-License-Application-with-Priority-Review-for-VYVGART-in-AChR-Ab-Seronegative-gMG.html
2. argenx Announces Positive Topline Results from ADAPT SERON Study of VYVGART in Patients with AChR-Ab Seronegative gMG. Argenx. August 25, 2025. Accessed January 13, 2025. https://argenx.com/news/2024/argenx-announces-positive-topline-results-from-adapt-seron-study
3. Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9