Science News: Early Promise for ANX005 as a Targeted Therapy in Guillain-Barré Syndrome
Published July 28, 2025
Science News
Submitted by: Abdullah AlQahtani, MD, MPH
Edited by: Oksana Sayko, MD
Citation: Mohammad QD, Islam Z, Papri N, Hayat S, Jahan I, Azad KAK, Artis DR, Hoehn B, Humphriss E, Lin P, Yednock T, Kroon HA. 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. J Peripher Nerv Syst. 2025 Mar;30(1):e70009. doi: 10.1111/jns.70009. PMID: 40000167; PMCID: PMC11886941
Summary: The Phase 1 study of ANX005, a C1q inhibitor, in Guillain-Barre Syndrome (GBS) patients without access to standard treatments (IVIg/PE) found that ANX005 was well-tolerated with no dose-limiting toxicities. The most common side effects were mild infusion-related rashes. Pharmacodynamically, ANX005 effectively inhibited C1q in serum and CSF and led to a reduction in a nerve damage marker (sNfL). Exploratory efficacy analysis suggested potential benefits, with more ANX005-treated patients showing improvement in disability scores (GBS-DS, ONLS) and muscle strength (MRC sum score), particularly in those receiving doses that inhibited C1q for at least one week.
The study shows that ANX005 shows promise as a targeted therapy for GBS by modulating the classical complement pathway. A phase 3 study is required.
Comments: This Phase 1 study explored the potential of ANX005, a C1q inhibitor, for treating Guillain-Barre Syndrome (GBS), an autoimmune neuropathy driven by the classical complement pathway. Existing treatments (IVIg/PE) have limitations and lack a targeted mechanism. The study in GBS patients without access to these treatments, conducted in Bangladesh where severe GBS is common, showed that ANX005 was well-tolerated with no dose-limiting toxicities; the main side effects waswere mild infusion-related rashes. ANX005 effectively inhibited C1q in both serum and cerebrospinal fluid (CSF),. It led to a significant reduction in serum neurofilament light chain (sNfL), a marker of nerve damage.
Exploratory efficacy suggested potential benefits: a higher proportion of ANX005-treated patients showed improvement in disability scores (GBS-DS, ONLS) and a faster increase in muscle strength (MRC sum score) compared to placebo. A proportional odds model also indicated a greater likelihood of improvement with ANX005.
In conclusion, this Phase 1 study supports further investigation of ANX005 as a targeted therapy for GBS due to its acceptable safety, effective C1q inhibition, reduction in a nerve damage marker, and encouraging early clinical outcomes. The selective targeting of the classical complement pathway by ANX005 may offer advantages over non-specific immunotherapies. A larger Phase 3 trial is underway to confirm these findings.