Efficacy and Safety of Efgartigimod Ph20 Sc in Adult Participants with Active Idiopathic Inflammatory Myopathy: Phase 2 Results from the ALKIVIA Study

Topic:

Clinical Trials

Poster Number: 408 O

Author(s):

Rohit Aggarwal, MD, MSc, University of Pittsburgh Medical Center, Todd Siluk, PharmD, argenx, Ghent, Belgium, Sebastian C. Rodriguez-Garcia, MD, MSc, argenx, Ghent, Belgium, Agna Neto, MD, argenx, Ghent, Belgium, Despoina Papadopoulou, MD, PhD, argenx, Ghent, Belgium, Ben Van Baelen, MSc, argenx, Ghent, Belgium, Paul Duncombe, BSc, PhD, argenx, Ghent, Belgium, Leentje De Ceuninck, PhD, argenx, Ghent, Belgium, Bas Van Der Woning, PhD, argenx, Ghent, Belgium, Hector Chinoy, FRCP, PhD, The University of Manchester, Manchester, UK

Background: Idiopathic inflammatory myopathy (IIM) is a rare, systemic, autoimmune, rheumatic disease with different subtypes, characterized by muscle weakness and extramuscular involvement. To date, no therapies treating different IIM subtypes are approved. Efgartigimod is a human immunoglobin G (IgG) 1 antibody Fc fragment engineered for increased affinity to the neonatal Fc receptor (FcRn) and uniquely contains only the part of the IgG antibody that normally binds FcRn. Objective: To evaluate the efficacy of subcutaneous (SC) efgartigimod (coformulated with recombinant human hyaluronidase PH20) vs placebo in patients with IIM.
Methods: ALKIVIA (NCT05523167) is an operationally seamless phase 2/3, randomized, double-blinded, placebo-controlled, parallel-group, multicenter study in adults with IIM. Randomized patients (1:1) received weekly efgartigimod PH20 SC or placebo in addition to background standard of care treatment for IIM. The primary endpoint was the 2016 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Total Improvement Score (TIS) at Week 24. This composite endpoint is based on improvement in Physician’s Global Disease Activity, Patient Global Disease Activity, Manual Muscle Testing-8, Health Assessment Questionnaire Disability Index, muscle enzymes, and Extramuscular Global Disease Activity. Results: The 24-week phase 2 study randomized 89 participants. Least-squares mean (LSM) TIS at Week 24 was statistically significantly higher in the efgartigimod PH20 SC arm than the placebo arm (LSM 50.45 vs 35.65, 2-sided P=0.0004). Individual components comprising the TIS also favored efgartigimod. Safety was comparable between treatment arms. Conclusion: ALKIVIA, the first study of an FcRn inhibitor in IIM, established proof of concept. The results demonstrate the mechanistic relevance of FcRn inhibition in IIM, indicating the potential pathogenicity of autoantibodies in IIM and supporting further evaluation of efgartigimod PH20 SC in the ongoing phase 3 part of the study.