FcRn blockade: a promising targeted treatment option for inflammatory idiopathic myopathy

Efgartigimod PH20 demonstrated significant clinical improvements in idiopathic inflammatory myopathy (IIM) in the phase 2 ALKIVIA trial, offering a novel mechanism of action with a favourable safety profile.

IIM, also called myositis, is a group of rare autoimmune diseases characterised by skeletal muscle inflammation and extra-muscular manifestations, potentially driven by IgG autoantibodies. “There is an unmet need in myositis for targeted therapy: we use too many steroids, and we need treatment options with a favourable corticosteroid-sparing effect and sustained response,” said Prof. Hector Chinoy (University of Manchester, United Kingdom) [1]. Efgartigimod PH20 is a human IgG1 antibody Fc fragment that selectively reduces IgG antibodies and pathogenic autoantibodies via FcRn blockade.

In the ALKIVIA phase 2 trial (NCT05523167), subcutaneous efgartigimod PH20 was evaluated in 89 adults with active dermatomyositis, immune-mediated necrotising myositis, polymyositis, or antisynthetase syndrome.

Participants, all of whom were on standard-of-care therapy, were randomised 1:1 to receive weekly efgartigimod PH20 or placebo. The primary endpoint was the total improvement score (TIS), defined by the 2016 ACR/EULAR myositis response criteria, at week 24.

Baseline participants' characteristics were balanced, with the majority of participants (>80%) being on oral corticosteroids and conventional DMARDs (>76%).

The mean TIS at week 24 was statistically significantly higher in the efgartigimod PH20 arm compared with placebo (50.45 versus 35.65, P=0.0004), meeting the primary endpoint. “First significant results were noted at week 8,” Prof. Chinoy added.

Key secondary endpoints reinforced these findings. In the active arm, significantly more patients achieved mild (TIS≥20: 91.5% vs 73.8%), moderate (TIS≥40: 78.7% vs 47.6%), and major (TIS≥60: 34.0% vs 9.5%) improvement, compared with placebo. “The high placebo response in the mild improvement is probably due to the background medication,” Prof. Chinoy said. Median time to TIS ≥20 and ≥40 was significantly shorter with efgartigimod than placebo (30 vs 71.5 days, P=0.0020; and 113 days vs not estimable, P=0.0293, respectively).

Safety outcomes were comparable between groups, with 87.2% of participants on the active arm versus 88.1% on placebo experiencing at least 1 adverse event (AE). The most common AEs were injection-site erythema, injection-site rash, and diarrhoea. Two deaths in the active arm were not drug-related.

The ALKIVIA study establishes proof of concept for FcRn inhibition in IIM, suggesting a critical role for autoantibodies in disease pathogenesis and offering a novel, targeted approach for treatment. These findings support further investigation in the ongoing phase 3 study.

1. Chinoy H, et al. Efficacy and safety of efgartigimod PH20 SC in adult participants with active idiopathic inflammatory myopathy: Phase 2 results from the ALKIVIA study. OP0002, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 18 June 2025