ARGX-119 Development
ARGX-119 is a humanized agonist mAb that specifically targets and activates MuSK to promote maturation and stabilization of the neuromuscular junction (NMJ). We plan to develop ARGX-119 in a range of neuromuscular diseases including CMS, a rare hereditary subtype of MG, ALS, and SMA, all severe neuromuscular indications.
NMJs are specialized synapses formed between motor neurons and muscle cells, which are essential for the ability to move and breathe. At the NMJ, motor neurons release acetylcholine, which binds to AChRs on the muscle to initiate muscle contraction. Deficits in the NMJ can cause neuromuscular disorders, which can range in severity from mild to life-threatening skeletal muscle weakness. MuSK is an essential component for the formation and function of NMJs.
ARGX-119 is the first and highly specific agonist mAb targeting human MuSK being developed for patients with neuromuscular disease, such as CMS and ALS. This mAb is derived from llamas and discovered using the argenx SIMPLE ANTIBODY™ platform technology. We developed ARGX-119 through our IIP program in collaboration with the world leading key opinion leaders on MuSK and the neuromuscular junction, including Professor Steve Burden from NYU and Professor Verschuuren from LUMC. In collaboration with Professor Burden, it was shown that ARGX-119 holds promising preclinical POC data in Dok7 congenital myasthenic syndrome, observed in a mouse model bearing the most common patient mutation and in ALS using ALS patient derived NMJ on-a-chip models. Based on these data, clinical development for ARGX-119 was initiated as activation of MuSK by ARGX-119 may stabilize, mature, and improve the function of the NMJ in patients with CMS or ALS, significantly reducing weakness and fatigability and improving quality of life.
A Phase 1 dose-escalation clinical trial in healthy volunteers was completed in 2024; data support advancement in POC studies.
A Phase 1b and 2a clinical trial in CMS and ALS respectively initiated in 2024 to assess early signal detection in patients. Early January 2025, we announced SMA as the third indication for ARGX-119 for which we expect to initiate a POC clinical trial in 2025.
Phase 1b Clinical Trial Design
The Phase 1b, multicenter, randomized, double-blinded, placebo-controlled clinical trial is designed to assess the safety, tolerability, PK, immunogenicity, and preliminary efficacy of ARGX-119 for the first time in participants with DOK7-CMS. The clinical trial is designed to demonstrate proof of biology for ARGX-119 through a preliminary evaluation of its efficacy with measures of muscle weakness and fatigability, activities of daily living, and patient-reported outcomes of global health in participants with DOK7-CMS. The clinical trial will be up to approximately 11 months long, comprising the following periods, a screening period: up to 28 days, a treatment period of 12 weeks and a follow-up period of approximately seven months. At baseline, eligible participants will be randomized in a 4:1 ratio to receive IV infusions of ARGX-119 or placebo. The primary objective is to evaluate the safety and tolerability of ARGX-119 in participants with DOK7 CMS. The secondary objective is to assess the PK, immunogenicity of ARGX-and efficacy of ARGX-119 in participants with DOK7 CMS.
Phase 2a reALiSe Clinical Trial Design
The ReALiSe clinical trial is a Phase 2a, double-blinded, randomized, placebo-controlled, and active-treatment extension clinical trial to assess the safety, tolerability, efficacy, pharmacokinetics, and immunogenicity of ARGX-119 in participants with amyotrophic lateral sclerosis. The clinical trial is designed to demonstrate proof of ARGX-119 activity through an evaluation of efficacy by assessing the impact of ARGX-119 on ALS disease outcomes, including muscle function in participants with ALS. Approximately 60 participants are planned to be enrolled, screened, and randomized 1:1:1:1 to one of three ARGX-119 intravenous dose arms or placebo IV for the double-blinded treatment period. This clinical trial will last up to 100 weeks. The clinical trial will contain the following periods: a screening period (up to four weeks), a double-blinded treatment period (24 weeks), an active-treatment extension period (48 weeks), and a safety-follow-up period (24 weeks). The primary objective is evaluate the safety and tolerability of ARGX-119 in participants with ALS. The secondary objective is to assess the efficacy of ARGX-119 on electrophysiological measures of disease progression in participants with ALS using MScan to measure motor unit number and other MScan‑derived neurophysiological markers. MScan provides parameters that have been associated with ALS disease progression (i.e., motor unit loss and/or enlarged motor units due to reinnervation). Additional exploratory outcome measures, including SVC and ALSFRS-R, will be used to explore ARGX-119 impact on ALS-relevant outcome measures.