argenx SE announced its decision to advance ARGX-119, a first-in-class agonist antibody targeting muscle-specific kinase (MuSK), to registrational studies for congenital myasthenic syndromes (CMS) following encouraging topline data from its Phase 1b clinical trial. The Amsterdam-based global immunology company's announcement marks a significant milestone for patients with this ultra-rare neuromuscular disorder that affects individuals from birth.
Phase 1b Study Demonstrates Proof-of-Concept
The Phase 1b multicenter, randomized, double-blinded, placebo-controlled trial evaluated ARGX-119 in patients with DOK7-CMS, a severe variant accounting for approximately 24% of CMS cases. The study met its primary endpoint of safety and tolerability while demonstrating consistent functional improvements across multiple secondary and exploratory efficacy measures.
"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," said Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx.
The 12-week treatment period showed consistent improvements in treated DOK7-CMS patients across multiple efficacy scores, including the Six-Minute Walk Test (6MWT), Quantitative Myasthenia Gravis (QMG) score, and Myasthenia Gravis Activities of Daily Living (MG-ADL) score. The clinical trial spanned approximately 11 months, including a screening period of up to 28 days, the 12-week treatment period, and a follow-up period of nearly seven months.
Addressing Critical Unmet Medical Need
Congenital Myasthenic Syndromes represent an ultra-rare and heterogeneous group of congenital neuromuscular disorders caused by genetic defects essential for neuromuscular junction integrity. The condition is characterized by early age of onset and fatigable muscle weakness, which can be debilitating and life-threatening, causing difficulties in speaking or swallowing, impaired or absent mobility, proximal arm and leg weakness, and respiratory insufficiency.
The prevalence of CMS is estimated at 5 per 1 million people, with DOK7-CMS affecting approximately 1.2 per 1 million individuals. Currently, there are no approved treatments for this condition, highlighting the significant unmet medical need that ARGX-119 aims to address.
Novel Mechanism of Action
ARGX-119 is a first-in-class humanized agonist monoclonal antibody that specifically targets and activates muscle-specific tyrosine kinase (MuSK) to promote maturation and stabilization of the neuromuscular junction. The antibody is derived from llamas and was discovered using argenx's SIMPLE Antibody™ platform technology.
The drug candidate is being developed for multiple neuromuscular diseases, including congenital myasthenic syndromes, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA). ARGX-119 was developed through argenx's Immunology Innovation Program in collaboration with leading experts including Professor Steven J. Burden from MGH, Professor Shohei Koide from NYU, and Professor Jan Verschuuren and Associate Professor Maartje Huijbers from LUMC.
Strengthening Innovation Pipeline
The advancement of ARGX-119 represents the sixth molecule developed through argenx's Immunology Innovation Program to demonstrate proof-of-concept, validating the company's collaborative discovery 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," said Peter Ulrichts, Ph.D., Chief Scientific Officer of argenx.
The Phase 1b study design included participants randomized 4:1 to receive intravenous ARGX-119 or placebo. All but one of the patients enrolled in the Phase 1b study also participated in an observational natural history study initiated by argenx in 2024 to better understand the CMS patient journey and disease burden, informing future development plans.
The company plans to present detailed results from the Phase 1b study at a future medical meeting, with the registrational study representing the next critical step toward potentially bringing the first approved treatment to patients with congenital myasthenic syndromes.
