argenx SE, a global immunology company, has announced its decision to move ARGX-119, a first-in-class agonist antibody targeting muscle-specific kinase (MuSK), into a registrational study for patients with congenital myasthenic syndromes (CMS). This advancement follows a positive analysis of topline data from its Phase 1b study, with detailed results to be presented at a future medical meeting. The move aligns with argenx's broader commitment to addressing the needs of patients with debilitating myasthenic disorders and reflects the strength of their Immunology Innovation Program (IIP).
The decision to progress ARGX-119 in CMS is directly supported by the favorable outcomes of the Phase 1b study. This multicenter, randomized, double-blinded, placebo-controlled trial primarily assessed the safety and tolerability of ARGX-119 in participants with DOK7-CMS, a specific and severe genetic form of CMS. The study successfully demonstrated a favorable safety and tolerability profile for ARGX-119. Beyond safety, the trial also evaluated efficacy through multiple secondary and exploratory endpoints, including the Six-Minute Walk Test (6MWT), Quantitative Myasthenia Gravis (QMG) score, and Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Consistent improvements were observed in treated DOK7-CMS patients across these efficacy scores throughout the 12-week treatment period. The trial also aimed to demonstrate proof-of-biology through assessments of muscle weakness, fatigability, daily activities, and patient-reported global health outcomes. Most patients in the Phase 1b study also participated in an argenx-initiated observational natural history study from 2024, providing valuable insights into the CMS patient journey and disease burden.
Congenital Myasthenic Syndromes (CMS) are an ultra-rare and diverse group of inherited neuromuscular disorders caused by genetic defects impacting the neuromuscular junction. These conditions are characterized by early onset and fatigable muscle weakness, which can be profoundly debilitating and even life-threatening, causing difficulties with speech, swallowing, mobility, and respiration. DOK7 variations are among the more common and severe causes, accounting for approximately 24% of CMS cases. Currently, there are no approved treatments for CMS, highlighting a significant unmet medical need for the estimated 5 per 1 million people affected globally (with DOK7-CMS affecting an estimated 1.2 per 1 million).
ARGX-119 is a humanized agonist monoclonal antibody (mAb) designed to specifically target and activate muscle-specific tyrosine kinase (MuSK). Its mechanism of action involves promoting the maturation and stabilization of the neuromuscular junction (NMJ), which is critical for proper muscle function. Discovered using argenx's proprietary SIMPLE Antibody™ platform technology, ARGX-119 is being developed for various neuromuscular diseases, including CMS, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA). Its development through argenx's IIP program involved collaborations with leading experts in MuSK and NMJ biology.
argenx, committed to translating immunology breakthroughs into novel antibody-based medicines, continues to build a world-class portfolio aimed at transforming the lives of individuals with severe autoimmune diseases.