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Complement-Targeting Agent ANX005 Demonstrates Therapeutic Efficacy in Phase 3 Study of Guillain-Barré Syndrome
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Key Takeaways
- ANX005 at 30 mg/kg significantly improved GBS patient outcomes, achieving primary and secondary endpoints in a phase 3 study.
- The treatment led to early functional improvements, reduced mechanical ventilation time, and improved walking independence.
Presented at the 2025 AAN Annual Meeting, findings from a phase 3 study showed that a single 30 mg/kg dose of ANX005 significantly improved health outcomes in Guillain-Barré syndrome, with benefits seen as early as week 1 and sustained over 6 months.
Quazi Deen Mohammad, MD, MBBS, FCPS
Data from a phase 3, double-blind, placebo-controlled study (NCT04701164) revealed that s single dose of investigational ANX005 (Annexon Biosciences) at 30 mg/kg doses led to significant and sustained improvement in patient health for those with Guillain-Barré syndrome (GBS) over a 6-month period. A biologics license application submission is expected to come in the first half of 2025, with ANX005 poised to potentially become the first approved therapy for GBS.1,2
Presented at 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9 in San Diego, California, the study featured 242 patients with GBS, at least 16 years of age, who were randomly assigned 1:1:1 to a single intravenous (IV) infusion of ANX005 at doses of either 30 or 75 mg, or placebo, for an 8-week treatment period. Results showed that both doses inhibited complement; however, only the 30 mg/kg dose group achieved the primary outcome of change in GBS Disability score (GBS-DS) trichotomy.
Led by Quazi Deen Mohammad, MD, MBBS, FCPS, a neurologist in Dhaka, Bangladesh, the trial featured only patients who were not receiving either intravenous immunoglobulin (IVIg) or plasma exchange. All told, those assigned to the ANX005 30 mg/kg 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. Notably, patients started to see improvements in function as early as week 1 of treatment (OR, 7.2; 95% CI, 3.07-16.96; P <.001).
An investigational treatment, ANX005 is a humanized IgG4 monoclonal antibody that binds with high affinity to the complement C1q protein and inhibits initiation of the classical complement cascade. Administered intravenously, the agent has also been tested in other conditions such as Huntington disease, autoimmune hemolytic anemia, and amyotrophic lateral sclerosis. To date, ANX005 has been granted fast track and orphan drug designations by the FDA, as well as orphan drug designation by the European Medicines agency.
By the end of the study period, 2.5-times more treated patients returned to normal health (OR, 4.1; 95% CI, 1.422-12.04; P = .0092) relative to placebo. In addition, these patients 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.
In terms of safety, the profiles of patients on the treatment were comparable across groups, with a balanced number of serious AEs observed. Overall, transient infusion-related reactions were found in 35.0% of treated patients with ANX005; however, this did not impact morality or infection rates. Investigators concluded that based on these findings, the agent has therapeutic potential to “transform” GBS management.
Positive data from the study was first reported in June 2024, with results showing that the 30 mg/kg group met its primary end point. In addition, that dosed group also demonstrated improvements vs placebo in a number of key secondary end points, including early gains in muscle strength by Medical Research Council (MRC) sum score at day 8 (P <.0001) and at week 8 (P = .0351). A prespecified analysis also revealed that ANX005 30 mg/kg resulted in a 31-day reduction in the median time to walk independently vs placebo (P = .0211). Furthermore, ANX005 also led to early reductions in serum levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage (11.2% reduction vs placebo between weeks 2-4; P = .03).3
Annexon also initiated a real-world evidence protocol with the International Guillain-Barr Syndrome Outcomes Study (IGOS) to establish comparability between phase 3 participants and Western patients, considering the trial was conducted in Bangladesh and Philippines. The IGOS study is a global, multicenter cohort that enrolled 2000 patients, tracking them for up to 3 years. A prespecified analysis showed that in Western patients with milder GBS, those treated with ANX005 30 mg/kg were 3 times more likely to achieve better health on GBS-DS at week 8 compared to placebo (P = 0.0102).
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REFERENCES
1. 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
2. Annexon Provides 2025 Outlook with Strong Momentum Accelerating into Breakthrough Year. News release. Annexon. January 13, 2025. Accessed April 4, 2025. https://ir.annexonbio.com/news-releases/news-release-details/annexon-provides-2025-outlook-strong-momentum-accelerating
3. Annexon Announces Positive Topline Results from Pivotal Phase 3 Trial for First-in-Class C1q Blocking Antibody ANX005 in Guillain-Barré Syndrome. News release. Annexon. June 4, 2024. Accessed April 4, 2025. https://ir.annexonbio.com/news-releases/news-release-details/annexon-announces-positive-topline-results-pivotal-phase-3-trial
