ANX005 Outperforms IVIg and Plasma Exchange in Improving Guillain-Barré Syndrome Outcomes

New data from the International GBS Outcome Study (IGOS) revealed that treatment with investigational ANX005 (Annexon) at 30 mg/kg doses led to more improved clinical outcomes in patients with Guillain-Barré syndrome (GBS) compared with intravenous immunoglobulin (IVIg) or plasma exchange (PE), considered the standard of care. Investigators noted that alternative matching and weighting methods will be explored as well.¹

Presented at the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20 in Edinburgh, Scotland, the analysis comprised ANX005-treated patients from a recent phase 3 trial (NCT04701164) who were matched 1:1 with non-Bangladeshi IGOS controls receiving IVIg/PE. In IGOS, 27% (500 of 1842) of patients were available for matching, although ultimately 65 were included. Similarly, 65 of the 79 patients (82%) from the phase 3 study were included, with this group generally younger with lower MRCss.

Led by Eveline Wiegers, a postdoctoral researcher in the Department of Neurology at the Erasmus MC University Medical Center, adequate balance was achieved for matching covariates but imbalance on mean age (GBS-02: 36 years; IGOS: 61 years) and time-from-onset (GBS-02: 6.3 days; IGOS: 4.5 days) remained. Using the GBS-DS, ANX-005-treated patients were found to be more likely to have better health state vs IVIg/PE at week 4 (outcome available in controls: 62/65; composite OR, 2.2; 95% CI, 0.8-6.0), week 8 (61/65: composite OR, 3.5; 95% CI, 1.3-9.1), and week 26 (53 of 65; composite OR, 2.2; 95% CI, 0.8-6.1).

ANX005, a humanized IgG monoclonal antibody that binds with high affinity to the complement C1q protein, has been in development for GBS, as well as other conditions like amyotrophic lateral sclerosis (ALS) and Huntington disease (HD). In the phase 3 study of GBS, 242 patients, at least 16 years of age, were randomly assigned 1:1:1 to a single intravenous infusion of ANX005 at doses of either 30 or 75 mg, or placebo, for an 8-week period. Notably, patients in the study were not receiving either IVIg or PE.

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Results from the study showed that the 30 mg/kg dose group was considered the most effective dose, as it was the only group to achieve its primary outcome of change in GBS-DS trichotomy. Those assigned to this group had 2.4-times greater odds of improved health at week 8 relative to placebo (OR, 2.4; 95% CI, 1.29-4.50; P = .0058), all while maintaining a safe profile. In addition, these patients started to see improvements in function as early as week 1 of ANX005 treatment (OR, 7.2; 95% CI, 3.07-16.96; P <.001).²

Patients on the 30 mg/kg doses also walked independently a median 31 days earlier (P = .0211) and spent a median 28 days less on mechanical ventilation (P = .0356) compared with placebo. Additionally, this group demonstrated improvements vs placebo in a number of key secondary end points, including early gains in muscle strength by MRC sum score at day 8 (P <.0001) and at week 8 (P = .0351). Notably, treatment with the complement-inhibiting therapy led to early reductions in serum levels of neurofilament light (NfL) chain (11.2% reduction vs placebo between weeks 2-4; P = .03).

At the 2023 American Academy of Neurology (AAN) Annual Meeting, data from a phase 2 study (NCT04514367) of ANX005 in patients with HD demonstrated the safety and potential efficacy of the agent in this population. In the study, patients received intravenous ANX005 every 2 weeks through week 22, with primary objectives that included safety/tolerability, pharmacokinetics (PK), and C1q, C4a, and NfL levels.³

The data showed that ANX005 resulted in complete and durable C1q inhibition in cerebrospinal fluid and serum, consistent with drug levels. Throughout the 9-month study, clinical progression was stable in treated patients, as measured by changes in composite Unified Huntington’s Disease Rating Scale (cUHDRS) and total functional capacity (TFC) relative to baseline. Subgroup analyses indicated that patients with high baseline C4a/C4 (n = 12) exhibited clinical improvement in cUHDRS at all timepoints, with a significant difference from patients with low baseline C4a/C4 (n = 11) at week 24 (P = .037). Furthermore, a trends of decreased cerebrospinal fluid YKL40 suggested a positive impact of ANX005 on microglial activity in patients exhibiting improved clinical response.

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REFERENCES
1. Wiegers E, Steyerberg E, Rajpar A, et al. Comparative Effectiveness In IGOS: ANX005 Versus Intravenous Immunoglobulin Or Plasma Exchange For Guillain-Barré Syndrome. Presented at: 2025 PNS Annual Meeting; May 17-20. Edinburgh, Scotland. Abstract O589.
2. Kroon HA, Islam Z, Collins P, et al. Efficacy and Safety of Targeted Immunotherapy with ANX005 in Treating Guillain-Barré Syndrome: A Phase 3 Multicenter Study. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA. ABSTRACT 004954
3. Kumar R, Claassen D, Mongan A, et al. A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD) (S32.009). Presented at: 2023 AAN Annual Meeting. Abstract S32.009.