New targeted therapy shows efficacy in inflammatory myopathy

Phase 2 results from the ALKIVIA trial suggest that efgartigimod PH20 leads to clinical improvement in idiopathic inflammatory myopathy (IIM) through neonatal fragment crystallisable receptor (FcRn) blockade, with a favourable safety profile. The study also confirms the critical role of autoantibodies in disease pathogenesis.

IIM, also known as myositis, is a heterogeneous group of autoimmune disorders characterised by skeletal muscle inflammation and extra-muscular manifestations, potentially driven by IgG autoantibodies [1]. “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) [2]. 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 myopathy, 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.

Figure: Efgartigimod led to a significant clinical improvement assessed by the TIS [2]



TIS, total improvement score.

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

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

Key secondary endpoints reinforced these findings. In the active arm, significantly more participants 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 explained. 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. The most common adverse events 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. Lundberg IF, et Nat Rev Dis Primers 2021;7:86.
2. Chinoy H, et 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 8 August 202522 August 2025