argenx Progresses Efgartigimod SC in Idiopathic Inflammatory Myopathies

argenx SE, a global immunology company based in Amsterdam, has decided to proceed with the development of efgartigimod subcutaneous (SC) in its ongoing Phase 2/3 ALKIVIA study. This decision follows the analysis of topline data from the Phase 2 portion. The ALKIVIA study targets idiopathic inflammatory myopathies (IIM), also known as myositis, and will continue enrolling patients across three specific subtypes: immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and dermatomyositis (DM).

Dr. Luc Truyen, Chief Medical Officer of argenx, highlighted the debilitating nature of idiopathic inflammatory myopathies, which cause muscle weakness and can affect multiple organs, severely impacting the quality of life, leading to increased morbidity and early mortality. He expressed optimism about the potential of efgartigimod SC to address the unmet needs of myositis patients, whose current treatment options are limited to steroids, plasma-derived therapies, and broad immunosuppressants. Dr. Truyen also thanked the patients and investigators participating in the ALKIVIA study and emphasized the goal of bringing efgartigimod to myositis patients as swiftly as possible.

The decision to continue the clinical development is backed by the efficacy and safety data from the Phase 2 portion of the ALKIVIA study. The study met its primary endpoint, showcasing a statistically significant treatment effect at Week 24 in mean total improvement score (TIS) compared to placebo. Additionally, improvements were observed across all six core set measures of the TIS, and the safety and tolerability profile was consistent with findings from other clinical trials.

The ALKIVIA study is designed as a randomized, double-blind, placebo-controlled, multicenter, operationally seamless Phase 2/3 trial. It aims to enroll a total of 240 patients and will observe these participants in two phases. The Phase 2 portion involves analysis after the first 90 patients complete the study, and the subsequent Phase 3 portion will ensue if a positive signal is observed. The main objective is to assess the mean total improvement score (TIS) at the end of the treatment period, which is 24 weeks for Phase 2 and 52 weeks for Phase 3, comparing treated patients (IMNM, ASyS, DM) to those on placebo. Secondary objectives include response rates, time to response, duration of response in TIS, and changes from baseline in individual TIS components. Further secondary endpoints assess quality of life and other functional scores.

Idiopathic inflammatory myopathies (myositis) are a group of rare autoimmune diseases that can either be muscle-specific or affect multiple organs such as the skin, joints, lungs, gastrointestinal tract, and heart. These diseases, known for causing significant disability and severely impacting quality of life, were initially classified as dermatomyositis (DM) or polymyositis. However, advancements in understanding their pathophysiology, including the identification of characteristic autoantibodies, have led to the recognition of new subtypes such as IMNM and ASyS. Common among all subtypes is proximal muscle weakness. IMNM involves muscle cell necrosis causing muscle weakness; ASyS features muscle inflammation, inflammatory arthritis, interstitial lung disease, thickening and cracking of the hands (referred to as "mechanic’s hands"), and Raynaud’s phenomenon. DM is marked by muscle inflammation and degeneration alongside skin abnormalities such as heliotrope rash, Gottron’s papules, erythematous, calcinosis, and edema.

Efgartigimod SC (efgartigimod alfa and hyaluronidase-qvfc) is a human IgG1 antibody fragment designed to reduce pathogenic immunoglobulin G (IgG) antibodies by binding to the neonatal Fc receptor (FcRn) and blocking the IgG recycling process. It is the first-approved FcRn blocker worldwide, marketed as VYVGART® Hytrulo in the U.S. and China for generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP), and as VYVGART SC or VYVDURA in Japan for gMG. Efgartigimod SC is currently being evaluated in over 15 severe autoimmune diseases where pathogenic IgGs are considered mediators of the disease.

argenx is dedicated to advancing the treatment of severe autoimmune diseases through innovative immunology research partnerships and aims to develop a robust portfolio of novel antibody-based medicines.