Efgartigimod alfa 1g/5.6ml solution for injection vials

BACKGROUND AND PURPOSE: Efgartigimod, a neonatal Fc receptor inhibitor, reduces IgG recycling and thus decreases pathogenic IgG autoantibody levels. This subpopulation analysis aimed to assess the efficacy, safety, and tolerability of subcutaneous efgartigimod PH20 in Chinese participants with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: ADHERE was a multistage, randomised-withdrawal, placebo-controlled phase II trial in adult participants with active CIDP. Eligible participants received open-label treatment with efgartigimod weekly for ≤12 weeks (Stage A) and those with confirmed evidence of clinical improvement (ECI) were randomised to receive double-blind treatment with efgartigimod or placebo weekly for ≤48 weeks (Stage B). Primary endpoints were proportion of participants with confirmed ECI (Stage A) and time to clinical deterioration as measured by adjusted Inflammatory Neuropathy Cause and Treatment score (Stage B). This descriptive analysis reports the results from the Chinese subpopulation. RESULTS: ADHERE enrolled 58 participants from mainland China for Stage A and of those, 47 were randomised (21 efgartigimod, 26 placebo) for Stage B. In Stage A, 45 (77.6%; 95% confidence interval [CI], 64.7%-87.5%) participants achieved confirmed ECI. In Stage B, median time to clinical deterioration was not reached with efgartigimod vs. 113.0 days (95% CI, 43.0-181.0 days) with placebo (hazard ratio, 0.313; 95% CI, 0.109-0.905). Across stages, most adverse events were mild or moderate, and no death occurred. No adverse events led to treatment discontinuation. CONCLUSIONS: Subcutaneous efgartigimod PH20 demonstrated clinical response and lowered the risk of clinical deterioration compared to placebo in Chinese participants with CIDP, while maintaining favourable safety and tolerability profiles.

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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia. Most patients with ITP have antiplatelet antibodies of the immunoglobulin G (IgG) subtype which through interaction with platelet and megakaryocyte glycoproteins result in increased platelet destruction and inhibition of platelet production. There are a variety of therapeutic options available for the treatment of ITP including corticosteroids, IVIgG, TPO-RA, rituximab, fostamatinib, and splenectomy. Long-term remissions with any of these therapies can vary widely and patients may require additional therapy. The neonatal Fc receptor (FcRn) plays a pivotal role in IgG and albumin physiology through recycling pathways. Efgartigimod is a human IgG1-derived fragment that has been modified by ABDEG technology to increase its affinity for FcRn at both physiologic and acidic pH. The binding of efgartigimod to FcRn blocks the interaction of IgG with FcRn facilitating increased lysosomal degradation of IgG and decreasing total IgG levels. Based on the mechanism of action and the known pathophysiology of ITP as well as the efficacy of other therapies such as intravenous immunoglobulin (IVIG), the use of efgartigimod in patients with ITP is attractive. This article will briefly discuss the pathophysiology of ITP, current treatments, and the data available on efgartigimod in ITP.

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Efgartigimod is a novel neonatal Fc receptor (FcRn) antagonist that reduces pathogenic immunoglobulin G (IgG) autoantibodies, offering a targeted therapeutic approach for generalized myasthenia gravis (gMG) and other antibody-mediated autoimmune diseases. This narrative review synthesizes clinical trial data, pharmacological insights, and real-world evidence to evaluate efgartigimod's efficacy, safety, and emerging applications. Phase 3 randomized controlled trials and extension studies demonstrate rapid and sustained improvements in muscle strength and patient-reported outcomes with a favorable safety profile, including reduced reliance on corticosteroids and intravenous immunoglobulin (IVIg). Additionally, observational studies highlight its expanding utility in diverse IgG-mediated disorders such as immune thrombocytopenia (ITP) and autoimmune encephalitis. Efgartigimod thus represents a paradigm shift in autoimmune disease management, enabling precision immunomodulation with the potential for broad clinical impact and improved patient quality of life (QOL).

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OBJECTIVES: Growing evidence exists about the pivotal role of immune mechanisms in the physiopathology of atrial fibrillation (AF). Drugs that modulate the immune system (immunomodulators) may contribute to the development of AF. We aimed to identify immunomodulators that are associated with AF to better define their safety profile, and elucidating their mechanisms of action could yield novel insights into AF's immune physiopathology. DESIGN: A descriptive and disproportionality analysis of claims data. SETTINGS: World pharmacovigilance database VigiBase until 1 March 2025. PRIMARY AND SECONDARY OUCTOMES: First, we ascertained the association of immunomodulators with AF over-reporting with a disproportionality analysis evaluating the multivariable-adjusted reporting odds ratio (aROR) for AF reporting performed for 141 immunomodulators in VigiBase. Then, a literature review was done to explore the underlying mechanisms of AF through immunomodulator mechanisms. RESULTS: A total of 6 148 556 reports encompassing at least one of the 141 immunomodulators were identified in Vigibase. Our primary analysis revealed 20 immunomodulators associated with AF over-reporting. The three immunomodulators with the greatest signal were: recombinant interleukin-11 with an aROR=20.91 (99.96% CI 12.08 to 36.17), efgartigimod alfa with an aROR=6.75 (99.96% CI 3.96 to 11.52) and recombinant interleukin-2 with an aROR=6.15 (99.96% CI 3.62 to 10.45). A derivative literature review posited a hypothetical immune 'vicious circle' promoting AF, involving T helper cells, macrophages and natural killer cells which could lead to electrophysiologic and histologic atrial remodelling. CONCLUSIONS: Twenty Food and Drug Administration (FDA)-labelled immunomodulators are associated with AF overreporting in Vigibase with a substantial signal on recombinant IL-11. These data contribute substantively to the prevailing understanding of the safety profile of these immunomodulators. Moreover, these findings support a multidirectional interaction between the immune system and AF development and might lead to considering future therapeutic targets. TRIAL REGISTRATION NUMBER: NCT06095791.

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Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity. Generalised myasthenia gravis (gMG) is a chronic, autoimmune neuromuscular disorder that can significantly impair quality of life. Several novel targeted therapeutic approaches have emerged to provide faster onset of action compared with conventional immunosuppressive therapy, favourable tolerability profile and the potential for a sustained disease control for patients with gMG. Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of gMG in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the pivotal clinical trial in patients with gMG, efgartigimod alfa rapidly reduced disease burden and improved muscle strength and quality of life. The beneficial effects of efgartigimod alfa occurred early and were durable and reproducible. Longer term, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa is generally well tolerated, with most adverse events being mild to moderate in severity. Thus, efgartigimod alfa is a novel, effective and generally well-tolerated treatment option for patients with gMG.

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Objective: Efgartigimod alfa, approved for treating generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive, has uncertain long-term safety in large populations This study analyzed adverse events (AEs) linked to efgartigimod alfa using data from the FDA Adverse Event Reporting System (FAERS). Methods: We collected and analyzed efgartigimod alfa-related reports from the FAERS database from the first quarter of 2022 through the second quarter of 2024. Disproportionality analysis was used in data mining to quantify efgartigimod alfa-related AE signals. Results: A total of 3,040 reports with efgartigimod alfa as the primary suspect and 12,487 AEs were retrieved from FAERS. The most frequently reported serious outcome was hospitalization (53.22%), and death occurred in 270 cases (8.88%). Disproportionality analysis detected 137 AE signals, with the most common in nervous system disorders (22.69%), general disorders and administration site conditions (16.90%), and infections and infestations (14.05%). Notably, in addition to infection-related AEs identified during clinical trials, this study detected unexpected signals, including inappropriate schedule of product administration (ROR 2.60, PRR 2.53, IC 1.34, EBGM 2.53) and nephrolithiasis (ROR 8.13, PRR 7.99, IC 2.99, EBGM 7.95). The median onset time of AEs was 81.0 days. Conclusion: Our study provides a comprehensive assessment of the post-marketing safety of efgartigimod alfa and highlights the need for continued vigilance regarding infection-related adverse events. Additionally, the detection of inappropriate schedules of product administration underscores the importance of enhanced training and pharmacist involvement in medication management. Further research is warranted to explore the potential association between efgartigimod alfa and nephrolithiasis.

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