argenx Reports Positive Phase 3 ALKIVIA Results for Efgartigimod in Autoimmune Myositis

argenx SE has announced positive topline results from the Phase 3 portion of the ALKIVIA study (NCT05523167), evaluating VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) in adults with autoimmune myositis. The study met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in disease activity in the combined population of patients with immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM).

At Week 52, efgartigimod produced a 15.4-point greater improvement in mean Total Improvement Score (TIS) compared with placebo (47.95 vs 32.56; p=0.0011). The findings also represent the first Phase 3 results to demonstrate a statistically significant treatment effect in IMNM, a myositis subtype with no approved targeted therapy.

Randomized Phase 3 Study of Efgartigimod

ALKIVIA is a global, randomized, double-blind, placebo-controlled, multicenter Phase 2/3 study evaluating subcutaneous efgartigimod in autoimmune myositis, including IMNM, DM and polymyositis. The study enrolled 264 patients with active disease receiving background treatment, who were randomized 1:1 to weekly efgartigimod PH20 SC or matched placebo.

Following analysis of the first 89 patients in the Phase 2 portion, the Phase 3 study enrolled 175 patients and incorporated a protocol-mandated corticosteroid taper. The Phase 3 primary endpoint was mean TIS at Week 52, with prespecified analyses of the combined IMNM and DM population and the individual subtypes.

Treatment Benefit Sustained Through Week 52

The treatment effect emerged early, with improvements over placebo observed from Week 4 and sustained through the full year of treatment, including during corticosteroid tapering.

In the prespecified IMNM analysis, efgartigimod produced a 14.8-point greater improvement in mean TIS compared with placebo at Week 52 (45.05 vs 30.24; p=0.0048), meeting the primary endpoint. This is particularly significant given the lack of approved targeted therapies for IMNM.

In the smaller DM cohort, efgartigimod produced a 14.5-point improvement over placebo (51.51 vs 36.96), although the difference did not reach statistical significance (p=0.1093). Across both IMNM and DM, all six core measures contributing to the TIS favored efgartigimod, covering muscle strength, physical function and disease activity. Improvement in skin disease activity was also observed in DM.

Consistent Safety and FcRn Targeting

Efgartigimod was well tolerated in the ALKIVIA study, with the observed safety profile consistent with prior studies and its established safety profile.

Efgartigimod is a human IgG1 antibody fragment that blocks the neonatal Fc receptor (FcRn), reducing circulating IgG autoantibodies. The approach is based on evidence that pathogenic IgG autoantibodies contribute to muscle fiber damage and extramuscular manifestations in autoimmune myositis.

Experts Highlight Clinical Significance

Luc Truyen, M.D., Ph.D., Chief Medical Officer at argenx, said the results represent the first Phase 3 evidence that precision targeting of FcRn with efgartigimod can provide meaningful benefit in autoimmune myositis. He highlighted the early and sustained treatment effect and its comparable magnitude across IMNM and DM, supporting the role of pathogenic IgG autoantibodies in the disease.

Rohit Aggarwal, M.D., M.S., Professor of Medicine and Co-Director of the Myositis Center at the University of Pittsburgh and an ALKIVIA investigator, emphasized the difficulty of achieving meaningful improvement in IMNM, where patients may have substantial irreversible muscle damage. He also noted the comparable magnitude of improvement observed in DM and the ongoing burden associated with chronic corticosteroid treatment.

 Implications for Myositis Treatment

The ALKIVIA findings provide clinical evidence supporting further development of efgartigimod as a potential targeted treatment for autoimmune myositis, particularly IMNM, where targeted treatment options remain unavailable.

However, efgartigimod is not currently approved for autoimmune myositis. The corticosteroid taper incorporated into the study provides important context for the findings, but the topline results do not establish a steroid-sparing benefit. Detailed ALKIVIA results are expected to be presented at an upcoming medical meeting and will provide additional information on efficacy and safety.

Efgartigimod continues to be evaluated in other autoimmune rheumatologic diseases, including Sjögren’s disease and systemic sclerosis.

Reference

argenx | argenx Announces Positive Topline Results from Phase 3 ALKIVIA Trial of Efgartigimod in Autoimmune Myositis