Efgartigimod in Rheumatology: Evaluating Its Impact on Myositis and Sjogren’s Disease

Argenx has unveiled promising Phase 2 results for efgartigimod in both idiopathic inflammatory myopathies (IIM) and primary Sjögren’s disease, presented at the European Congress of Rheumatology (EULAR) 2025. These findings, alongside the U.S. FDA's Fast Track designation for efgartigimod in primary Sjögren’s, mark a significant advancement in targeted therapies for autoimmune diseases.

In the ALKIVIA study, a randomized, double-blind, placebo-controlled Phase 2/3 trial, efgartigimod demonstrated substantial improvements in muscle strength and physical function among patients with myositis, encompassing subtypes such as immune-mediated necrotizing myopathy, anti-synthetase syndrome, and dermatomyositis. Patients treated with efgartigimod achieved a mean Total Improvement Score (TIS) of 50.45, compared to 35.65 in the placebo group (P=0.0004). Notably, 79% of these patients experienced moderate improvement, and 34% achieved major improvement. The onset of minimal improvement was observed within 30 days, with moderate improvement by 16 weeks. The safety profile was favorable, with treatment-emergent adverse events comparable between the efgartigimod and placebo groups.

Dr. Hector Chinoy, a principal investigator of the ALKIVIA study and Professor of Rheumatology and Neuromuscular Disease at The University of Manchester, remarked, “Results from this study, the first of an FcRn inhibitor in myositis, demonstrate the potential of a transformative targeted treatment approach.”

In the RHO study, a Phase 2 proof-of-concept trial for primary Sjögren’s disease, efgartigimod achieved a 45.5% response rate on the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) at Week 24, significantly outperforming the 11.1% response in the placebo group. The treatment led to a rapid and sustained reduction in total IgG levels (~60% from Week 4 onwards) and notable decreases in disease-associated autoantibodies, including anti-Ro52 (-57% vs. +13% in placebo) and rheumatoid factor (-26.6% vs. -5.3%). Additionally, reductions in C1Q immune complexes were observed. Efgartigimod was well-tolerated, with no new safety signals identified.

These compelling results have led the FDA to grant Fast Track designation to efgartigimod for the treatment of primary Sjögren’s disease, acknowledging the urgent need for effective therapies in this area. Argenx is advancing to a Phase 3 trial, UNITY, to further evaluate the efficacy and safety of efgartigimod in patients with moderate to severe primary Sjögren’s disease .

Efgartigimod, marketed as Vyvgart, is an FcRn inhibitor that reduces pathogenic IgG antibodies by blocking their recycling, thereby lowering circulating levels. Its mechanism of action offers a targeted approach to treating autoimmune diseases by addressing the underlying pathophysiology rather than merely alleviating symptoms.

With ongoing Phase 3 studies in both myositis (ALKIVIA) and primary Sjögren’s disease (UNITY), Argenx is poised to potentially introduce a novel, precision therapy for patients with these challenging autoimmune conditions.