argenx Advances ARGX-119 into Registrational Study for Congenital Myasthenic Syndromes Following Positive Phase 1b Data
argenx SE (Euronext & Nasdaq: ARGX), a global immunology company focused on improving outcomes for patients with severe autoimmune diseases, has announced plans to progress its investigational therapy ARGX-119 into a registrational clinical trial for congenital myasthenic syndromes (CMS). The decision follows an analysis of topline data from a Phase 1b clinical study, which demonstrated encouraging safety and efficacy results in patients with DOK7-CMS, one of the more severe and prevalent subtypes of this ultra-rare neuromuscular disorder. Detailed data from the trial will be shared at an upcoming medical conference.
ARGX-119 is a first-in-class agonist antibody that targets muscle-specific kinase (MuSK), a protein critical to the function of neuromuscular junctions. By enhancing MuSK activity, ARGX-119 aims to improve neuromuscular transmission and muscle strength in patients with CMS, a condition that often begins in infancy and leads to lifelong disability.
Dr. Luc Truyen, Chief Medical Officer of argenx, emphasized the significance of the development milestone, stating, “The results of our Phase 1b ARGX-119 study in congenital myasthenic syndromes, an ultra-rare disorder that affects patients from birth, builds on our experience and understanding of myasthenic disorders and aligns with our aspiration to serve even more patients living with these debilitating diseases.”
Peter Ulrichts, Ph.D., Chief Scientific Officer of argenx, highlighted the broader impact of the company’s research model: “ARGX-119 is the sixth molecule developed through our Immunology Innovation Program to show proof-of-concept, reflecting the strength of our innovation model where our deep knowledge of the biology and expertise in antibody engineering come together to push the boundaries of what’s possible. argenx remains focused on uncovering new biological insights into misunderstood diseases to meaningfully change the lives of patients who have long-been underserved.”
Promising Results from Phase 1b Trial
The Phase 1b study was a multicenter, randomized, double-blind, placebo-controlled clinical trial specifically designed to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of ARGX-119 in individuals with DOK7-related CMS.
Participants were randomized in a 4:1 ratio to receive either intravenous ARGX-119 or placebo over a 12-week treatment period, following a screening phase of up to 28 days. The study also incorporated a nearly seven-month follow-up period to evaluate long-term effects.
The primary objective of the trial was to evaluate the safety and tolerability of ARGX-119. According to the topline data, ARGX-119 was well tolerated by patients, meeting the study’s primary endpoint. Secondary and exploratory objectives included measures of clinical efficacy, which were assessed through a range of functional and patient-reported outcome measures.
These included:
- Six-Minute Walk Test (6MWT) – an established metric to evaluate endurance and functional mobility
- Quantitative Myasthenia Gravis (QMG) Score – a physician-assessed tool measuring muscle strength
- Myasthenia Gravis Activities of Daily Living (MG-ADL) Score – a patient-reported measure reflecting disease impact on daily life
Patients receiving ARGX-119, particularly those with DOK7 mutations, showed consistent improvements across these efficacy endpoints over the 12-week treatment window.
Importantly, nearly all participants in the Phase 1b trial had previously enrolled in an observational natural history study initiated by argenx in 2024. This foundational research effort provided valuable baseline insights into the disease burden and progression of CMS, thereby helping to inform the design and evaluation of ARGX-119’s clinical development program.
Understanding Congenital Myasthenic Syndromes (CMS)
Congenital myasthenic syndromes represent a highly heterogeneous group of inherited neuromuscular disorders characterized by defects in proteins essential to the structure and function of the neuromuscular junction. These genetic abnormalities disrupt the communication between nerves and muscles, resulting in fatigable muscle weakness and functional impairment that often begins at birth or in early childhood.
CMS symptoms can range from mild to life-threatening and may include:
- Weakness of limbs, especially proximal muscles
- Difficulty swallowing or speaking
- Poor mobility or inability to walk
- Respiratory insufficiency
Among the various subtypes, DOK7-CMS is one of the more prevalent and severe forms, responsible for approximately 24% of all CMS cases. Despite the seriousness of this condition, no approved disease-specific therapies currently exist. Standard treatment often includes symptomatic management and off-label use of medications that may offer limited benefit.
The estimated prevalence of CMS is around 5 cases per 1 million people, with DOK7-CMS comprising about 1.2 per 1 million. These statistics highlight the urgency for novel therapies that directly target the underlying biology of the disease.
Next Steps for ARGX-119
Following the encouraging Phase 1b data, argenx plans to advance ARGX-119 into a registrational clinical study. This pivotal trial will further evaluate the therapy’s long-term safety, efficacy, and potential for regulatory approval in patients with CMS, focusing particularly on the DOK7 subtype.
ARGX-119’s progress marks a meaningful step forward for patients with ultra-rare neuromuscular disorders who currently have limited or no targeted treatment options. It also reinforces argenx’s commitment to leveraging its Immunology Innovation Platform to bring transformative therapies to patients across a broad spectrum of underserved autoimmune and neuromuscular conditions.
