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Clinical Trial
. 2025 Mar;30(1):e70009.
doi: 10.1111/jns.70009.

Results From a Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ANX005, a C1q Inhibitor, in Patients With Guillain-Barré Syndrome

Quazi Deen Mohammad  1 , Zhahirul Islam  2 , Nowshin Papri  2   3 , Shoma Hayat  2 , Israt Jahan  2 , Khan Abul Kalam Azad  4 , Dean R Artis  5 , Benjamin Hoehn  5 , Eric Humphriss  5 , Ping Lin  5 , Ted Yednock  5 , Henk-André Kroon  5
Affiliations
Clinical Trial

Results From a Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ANX005, a C1q Inhibitor, in Patients With Guillain-Barré Syndrome

Quazi Deen Mohammad et al. J Peripher Nerv Syst. 2025 Mar.

Erratum in

Abstract

Background and aims: Guillain-Barré syndrome (GBS) is an acute autoimmune peripheral neuropathy driven by autoantibodies and classical complement pathway activation. Despite treatments with intravenous immunoglobulin or plasma exchange, GBS remains characterized by variability in recovery and high incidence of residual disabilities. This randomized, double-blind, placebo-controlled Phase 1 trial evaluated the safety, tolerability, and pharmacokinetics of ANX005, a novel therapeutic targeting the classical complement cascade.

Methods: Patients with recent-onset GBS, who had no access to intravenous immunoglobulin or plasma exchange, received escalating doses of ANX005 or placebo as a single IV infusion. Primary objectives included assessments of safety. Secondary objectives included determination of pharmacokinetic and pharmacodynamic profiles and clinical outcomes through Week 8. Exploratory objectives included an evaluation of serum and cerebrospinal fluid (CSF) complement and tissue damage biomarkers.

Results: Fifty patients were randomized to receive either ANX005 (n = 38) or placebo (n = 12). ANX005 was well-tolerated across all doses with no dose-limiting toxicities, suggesting an acceptable safety profile. Pharmacodynamic data showed effective C1q inhibition and a reduction in neurofilament light chain levels, suggesting nerve damage mitigation. Exploratory endpoints evaluating clinical outcomes included improvements in Medical Research Council sum scores, GBS-Disability Score, and Overall Neuropathy Limitations Scale with ANX005 compared to placebo, particularly in patients receiving doses that inhibited serum C1q for ≥ 1 week and provided C1q blockade in the CSF.

Interpretation: These results support ANX005 as a targeted therapy for GBS that modulates the classical complement pathway. Further investigation in a larger Phase 3 trial is warranted to confirm these results and assess the long-term benefits of complement inhibition in patients with GBS.

Keywords: ANX005; C1q; Guillain–Barré syndrome; Phase 1; complement.

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Conflict of interest statement

Quazi Deen Mohammad reports a consultancy/advisory role with Annexon Biosciences. Zhahirul Islam reports research funding from Fogarty International Center, National Institute of Neurological Disorders and Stroke of the National Institutes of Health, USA, and Annexon Biosciences. Nowshin Papri, Shoma Hayat, Israt Jahan, and Khan Abul Kalam Azad report no disclosures relevant to the manuscript. Dean R. Artis and Benjamin Hoehn are employees of Annexon Biosciences. Eric Humphriss is a former employee and shareholder of Annexon Biosciences. Ted Yednock is an employee of Annexon Biosciences and holds equity ownership in Annexon Biosciences. Henk‐André Kroon is an employee and shareholder of Annexon Biosciences.

Figures

FIGURE 1
FIGURE 1
Patient populations and analyses. GBS‐DS, Guillain–Barré Syndrome‐Disability Score; ICU, intensive care unit; MRC, Medical Research Council; NfL, neurofilament light chain; PD, pharmacodynamics; PK, pharmacokinetics.
FIGURE 2
FIGURE 2
Mean free ANX005 in serum following single doses (n = 38).
FIGURE 3
FIGURE 3
Free C1q levels in serum (n = 38).
FIGURE 4
FIGURE 4
Free C1q levels in CSF by treatment (n = 26). CSF, cerebrospinal fluid.
FIGURE 5
FIGURE 5
(A) NfL serum levels Weeks 2–4 in placebo‐ versus ANX005 18–75 mg/kg‐treated patients (n = 26). (B) Percentage change in NfL levels Weeks 2–4 in placebo‐ versus ANX005 18–75 mg/kg‐treated patients (n = 26). NfL, neurofilament light chain.
FIGURE 6
FIGURE 6
(A) Dichotomous efficacy outcome measures at 8 weeks: Ability to run (GBS‐DS 0, 1) or gain in GBS‐DS by ≥ 3 points (n = 26). (B) Proportional odds of improvement in GBS (n = 26). (0.53, 15.1), nonsignificant p‐value. To calculate PO, one patient is needed within each category. Given no placebo patients made it to the good state of health category, a conservative imputation method was used, and one placebo patient was added to the good state of health category to generate a PO. N = 27: ANX005 18–75 mg/kg (n = 18), placebo (n = 9). PO, proportional odds.
FIGURE 7
FIGURE 7
Change in MRC from baseline for ANX005 and placebo (N = 26). MRC, Medical Research Council.
FIGURE 8
FIGURE 8
MRC sum score stratified by MRC score ≤ 20 and > 20 (N = 50). MRC, Medical Research Council.
See this image and copyright information in PMC

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