Argenx Commences Second Cohort of Phase 2 ARDA Study for Empasiprutant in Multifocal Motor Neuropathy
Tuesday, June 20, 2023
Argenx SE, a global immunology company listed on Euronext and Nasdaq under the ticker symbol ARGX, has recently announced its strategy to advance to a second dose cohort in the Phase 2 ARDA study of empasiprubart (ARGX-117) for the treatment of multifocal motor neuropathy (MMN). This decision comes after an interim analysis of the first dose cohort conducted by an Independent Data Monitoring Committee (IDMC) on June 19, 2023.
The company expressed satisfaction with the favorable safety profile and initial efficacy signals observed in the ARDA study. The IDMC's recommendation to proceed to the next cohort further supports their optimism. Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx, acknowledged the significant burden faced by individuals suffering from MMN, a chronic autoimmune disease characterized by progressive muscle weakness. The mission of argenx is to transform treatment options for autoimmune patients by challenging conventional expectations. Based on the promising safety and efficacy data observed thus far, the company believes that empasiprubart, a first-in-class C2 inhibitor, has the potential to achieve this goal in MMN and other autoimmune indications.
The IDMC reviewed interim safety data from all 22 patients enrolled in the first cohort of the ARDA study, including nine patients who completed the full 16-week treatment period. The committee confirmed the favorable safety and tolerability profile of empasiprubart, consistent with the results from the Phase 1 study, and recommended moving forward to the second cohort. An early assessment of efficacy in all 22 patients demonstrated proof-of-concept for empasiprubart in MMN, with clear differentiation observed between treated patients and those receiving a placebo across various clinical outcome measures, including time to IVIg retreatment.
The ARDA study plans to enroll a total of 48 patients in two cohorts. Its objectives include assessing the safety, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of empasiprubart and generating data to inform the dose selection for the Phase 3 study. Following the IDMC's recommendation, argenx intends to build upon the promising results from the first cohort by evaluating a higher dose level of empasiprubart in the second cohort.
The Phase 2 ARDA study is a randomized, double-blinded, placebo-controlled multicenter trial involving adults with MMN. It consists of an initial period to evaluate IVIg dependency and monitor patients, followed by two 16-week treatment cohorts. In each cohort, 24 MMN patients will be randomized in a 2:1 ratio to receive either empasiprubart or placebo. The primary endpoint of the study is safety and tolerability, and additional endpoints include time to IVIg retreatment, biomarker analysis of C2 levels, changes in clinical efficacy scores, and patient-reported quality of life measures.
Empasiprubart (ARGX-117) is a humanized sweeping antibody that specifically binds to C2, effectively blocking both the classical and lectin pathways of the complement cascade. By targeting upstream complement activity, empasiprubart has the potential to reduce tissue inflammation, presenting a broad pipeline opportunity for treating severe autoimmune conditions. In addition to MMN, argenx plans to explore the efficacy of empasiprubart in delayed graft function following kidney transplant and dermatomyositis.
Multifocal motor neuropathy (MMN) is a rare autoimmune disease characterized by chronic peripheral nervous system impairment. Patients with MMN experience gradually progressive, asymmetric muscle weakness, primarily affecting the hands, forearms, and lower legs. The disease is often associated with anti-GM1 IgM autoimmunity, leading to activation of the classical complement pathway and subsequent axon damage. High-dose intravenous immunoglobulin (IVIg) is the only approved treatment for MMN, but patients commonly experience disease progression despite therapy, highlighting the need for more effective and well-tolerated therapeutic options.
