Real-World Data Reveal Concern of Infections in Efgartigimod for Myasthenia Gravis

Elisabetta Poluzzi, PhD, PharmD

Data from more than 5000 reports from the FDA Adverse Event Reporting System (FAES) showed that infections were a concern for patients with myasthenia gravis (MG) treated with efgartigimod (Vyvgart; argenx) or immunoglobulins, accounting for more than one-third of cases for efgartigimod. In addition, findings demonstrated a higher likelihood of serious infections and hospitalization in efgartigimod vs immunoglobulins.¹

Presented at the 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9 in San Diego, California, infections represented 37% (n = 557) of the reports for efgartigimod vs 24% (n = 107) of those for immunoglobulins. Patients on efgartigimod, a neonatal fragment crystallizable receptor (FcRn) inhibitor, were more likely to have serious infectious events (92% vs 70.65%) and to result in hospitalization (52% vs 23.72%) than for immunoglobulins.

Led by Elisabetta Poluzzi, PhD, PharmD, a professor in the Department of Medical and Surgical Services, University of Bologna, the data comprised of 5643 reports from the FAES from 2022-2023. Among these, reports suspected to efgartigimod and immunoglobulins accounted for 1499 and 443 events, respectively. All told, in the disproportionality analysis for the period 2022-2023, only 1 signal emerged for immunoglobulins, while 12 signals were identified for efgartigimod alfa related to various types of infections, including respiratory and viral infections.

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Efgartigimod was first approved for the treatment of generalized MG in adults who are anti-acetylcholine receptor (AChR) antibody-positive in December 2021, marking its first approval.² Years later, in 2023, the FDA expanded its indication to treat primary immune thrombocytopenia (ITP) in adults who have had insufficient response to previous treatments.³ In addition, during that same year, the agency also gave greenlight to a subcutaneous formulation of efgartigimod. More recently, in mid-2024, the drug gained another expanded indication for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP).⁴

Josh Bryson

The findings from Poluzzi et al. should be taken with caution, as Josh Bryson, head of U.S. Medical Affairs at argenx, noted. "The FDA makes it clear on their FAES portal that there are limitations to this data that should be considered in reference to this abstract. Because the data is not perfect, is incomplete, contains duplicates, and some of the events were not causally attributed, there are limitations."

Bryson added, "They have a very specific disclaimer that the data should not be used to make comparative safety claims versus other products. While we do think it's a really important tool—and is something we respect from a pharmacovigilance perspective—this is an important limitation to outline."

Efgartigimod’s original approval in MG was based on data from the phase 3 ADAPT trial (NCT03669588) and its clinical profile was further studied in the ADAPT+ open-label extension (OLE), lasting up to 3 years. In the OLE, patients received efgartigimod treatment in cycles of 4 intravenous infusions at 10 mg/kg per week. In terms of the safety of efgartigimod, treatment-emergent AEs were reported in 84.8% (n = 123) of patients, the most being headache (24.8%), COVID-19 (15.2%), and nasopharyngitis (13.8%).⁵

Overall, serious treatment-emergent AEs (TEAEs) were found in 23.4% (n = 34) of patients, with fatal TEAEs representing 3.4% (n = 5) of the cohort. In addition, any infections, considered AEs of special interest (AESI), were found in 55.2% (n = 80) of patients in the OLE, with infusion-related reactions also occurring in 10.3% (n = 15) of participants. Notably, none of the TEAEs with fatal outcomes were considered to be related to efgartigimod treatment, as assessed by the trial investigators.

Bryson continued, "This abstract considers infections and hospitalizations. We think it's important that if neurologists or HCPs are making treatment decisions with patients, that they refer to the core labels for the products which describe the risk benefits beyond infections. It is an important consideration between patients and their treaters."

He added, "We continue to release data in these indications. we continue to generate more data in both a clinical and real-world setting, and we hope that as longer term data comes out, we can continue to inform clinicians on the best way to manage their patients with these serious, chronic diseases."

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REFERENCES
1. Giunchi V, Fusaroli M, Baquié M, Wissman C, Poluzzi E, et al. Infections-related Safety Profile of Efgartigimod Alpha and Immunoglobulins in Myasthenia Gravis (S34.003). Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, California. Abstract 34.003.
2. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed April 10, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis
3. argenx Announces Approval of VYVGART (efgartigimod alfa) in Japan for Adults with Primary Immune Thrombocytopenia. News release. Argenx. March 26, 2024. Accessed April 10, 2025. https://us.argenx.com/news/2024/argenx-announces-approval-vyvgart-efgartigimod-alfa-japan-adults-primary-immune
4. argenx Announces FDA Approval of VYVGART Hytrulo for Chronic Inflammatory Demyelinating Polyneuropathy. News release. Argenx. June 21, 2024. Accessed April 10, 2025. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy
5. Howard JF, Bril V, Vu T, et al. Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis. Front Neurol. 2024;17(14):1284444. doi:10.3389/fneur.2023.1284444