Efgartigimod Offers Benefit in Seronegative Generalized Myasthenia Gravis

Efgartigimod led to significant improvements in disease severity and daily functioning among patients with double-seronegative generalized myasthenia gravis (MG), according to results from a 6-month prospective, open-label study.¹ The findings address a long-standing evidence gap in a subgroup of MG patients who often experience refractory disease and limited therapeutic options.

“Our results, which showed a significant reduction in the [Myasthenia Gravis Impairment Index] at the study endpoint compared to baseline, achieved the primary outcome of the study,” wrote investigators, led by Vera Bril, MD, from the Ellen and Martin Prosserman Centre for Neuromuscular Diseases, University Health Network at the University of Toronto. “Improvements were observed in other MG scores, including [Myasthenia Gravis Activities of Daily Living], [Myasthenia gravis quality of life-revised], [single simple question], and [patient-acceptable symptom state], strengthening the results.”¹

Efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, is approved for patients with acetylcholine receptor antibody (AChRAb)–positive generalized MG based on the ADAPT trial, but evidence in patients without AChR or muscle-specific tyrosine kinase (MuSK) antibodies remains limited. Seronegative MG accounts for approximately 15% of generalized MG cases and is often associated with greater rates of treatment resistance and persistent disease burden.²

To address this gap, investigators conducted a 6-month, single-center, open-label study evaluating the safety and efficacy of efgartigimod in adults with double-seronegative generalized MG who remained symptomatic despite stable standard-of-care therapy.¹ The study enrolled 30 patients aged ≥ 18 years with clinical and electrodiagnostic features of MG and negative testing for AChR and MuSK antibodies. Participants had moderate to severe disease at baseline, with a mean Myasthenia Gravis Impairment Index (MGII) score of 44.6 and a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 10.6. Most patients were considered treatment resistant, failing a median of 2 prior immunosuppressive or immunomodulatory therapies.

Patients received intravenous efgartigimod 10 mg/kg weekly for 4 weeks, followed by biweekly dosing for 5 months. The primary endpoint was the change from baseline in MGII at 6 months, with secondary endpoints including MG-ADL, responder rates, patient-reported outcomes, and safety.

Efgartigimod led to a statistically significant improvement in MGII at 6 months. At weeks 30–31, MGII scores decreased by a mean of 11.92 points compared with baseline (P <.001), exceeding the established minimal clinically important difference.¹

Consistent improvements were also observed in secondary endpoints. The MG-ADL score improved by a mean of 3.4 points at weeks 30 and 31 (P <.001), reflecting better performance in daily activities. Overall, 72% of patients met responder criteria based on MGII improvement, with 31% classified as early responders who demonstrated clinically meaningful improvement within the first 4 weeks of treatment.¹

Additional patient-reported outcomes, including quality-of-life measures and patient-acceptable symptom state, also improved over the treatment period, although no patients achieved complete symptom remission.

Efgartigimod was generally well tolerated in this seronegative MG population. Among the sample, 83.3% experienced adverse events, with most being mild. The common adverse events included headache, flu-like symptoms, and urinary tract infections. Investigators observed no new safety signals nor treatment discontinuation due to adverse events.¹

Although limited by its open-label design and small sample size, the study provides prospective evidence supporting the efficacy of FcRn inhibition in seronegative generalized MG. The magnitude of improvement across MGII and MG-ADL, along with a high responder rate, suggests a true treatment effect rather than a placebo response alone.

“The results indicate that the novel selective IgG reduction mechanism by blocking the FcRn receptor with efgartigimod is well tolerated and effective in SN MG patients,” investigators concluded.¹

References

1. Khateb M, Sivadasan A, Barnett-Tapia C, et al. Open-label study of efgartigimod in seronegative myasthenia gravis. Ther Adv Neurol Disord. 2025;18:17562864251388019. Published 2025 Oct 31. doi:10.1177/17562864251388019

2. Soliven BC, Lange DJ, Penn AS, et al. Seronegative myasthenia gravis. Neurology. 1988;38(4):514-517. doi:10.1212/wnl.38.4.514