Efficacy and Safety of Targeted Immunotherapy with ANX005 in Treating Guillain-Barré Syndrome: A Phase 3 Multicenter Study
Henk-Andre Kroon1, Zhahirul Islam2, Peter Collins1, Benjamin Hoehn1, Eric Humphriss1, Ping Lin1, Glenn Morrison1, Jose Navarro3, Khan Abul Kalam Azad4, Dean R Artis1, Ted Yednock1, Quazi Deen Mohammad5
1Annexon Biosciences, 2Laboratory of Gut-Brain Axis, icddr,b, 3José R. Reyes Memorial Medical Center, 4Dhaka Medical College and Hospital, 5National Institute of Neuroscience (NINS)
Objective:
Evaluate the efficacy and safety of ANX005 compared to placebo in Guillain-Barré syndrome (GBS) patients.
Background:
GBS is an acute autoimmune disorder. An infection triggers antibodies that cross-react with gangliosides on peripheral nerve components, activating C1q and the classical complement pathway, leading to neuroinflammation and nerve damage. ANX005, a monoclonal antibody inhibiting C1q, blocks classical complement pathway activation.
Design/Methods:
This phase 3, double-blind, placebo-controlled study (NCT04701164) evaluated 242 GBS patients, aged ≥16 years with GBS disability score (GBS-DS) of 3, 4, or 5, randomized 1:1:1 to a single IV infusion of ANX005 (30 or 75 mg/kg) or placebo, without receiving either IVIg or plasma exchange. Stratification was by muscle strength and time from onset of weakness to infusion. The primary outcome measure was GBS-DS trichotomy at 8 weeks.
Results:
Both doses inhibited complement, although ANX005 30 mg/kg met the primary endpoint while the 75 mg/kg dose did not. Patients receiving ANX005 30 mg/kg had 2.4-times higher odds of improved health at Week 8 compared to placebo (odds ratio [OR] 2.4, 95% CI 1.29-4.50; p=0.0058). Improved function was evident by Week 1 (OR 7.2, 95% CI 3.07-16.96; p<0.001). By study completion, 2.5-times more treated patients returned to normal health (OR 4.1, 95% CI 1.422-12.04; p=0.0092) versus placebo. These patients also walked independently a median 31 days earlier (p=0.0211) and spent a median 28 days less on mechanical ventilation (p=0.0356) compared to placebo. Safety profiles were comparable across groups, with serious adverse events balanced. Transient infusion-related reactions occurred in 35.0% of patients treated with ANX005, with no impact on mortality or infection rates.
Conclusions:
A single dose of ANX005 30 mg/kg rapidly inhibited C1q, leading to a significant and sustained improvement in patient health over 6 months versus placebo, and was generally well-tolerated. ANX005 has the potential to transform GBS management.
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