Abstract Details

Title Effect of Combined Intravenous Immunoglobulin and Classical Complement Inhibitor ANX005 in Guillain-Barré Syndrome

Topic Autoimmune Neurology

Presentation(s) S25 - Autoimmune Neurology 2: Clinical Trials and Treatment (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Background GBS is an antibody-mediated autoimmune disease, with peripheral neuronal damage mediated by classical complement pathway (CCP) activation. ANX005 is a humanized monoclonal antibody inhibiting C1q, the initiator molecule of the CCP. ANX005 has demonstrated target engagement in blood and CSF, reduction of serum neurofilament light chain (sNfL) and complement activation markers in patients with GBS.

Objective To assess the impact of combination intravenous immunoglobulin (IVIg) and ANX005 in Guillain-Barré Syndrome (GBS) patients from Bangladesh and Denmark.

Design/Methods A phase 1b open-label study (26-week duration) assessing safety, pharmacokinetics (PK), pharmacodynamics, and outcome in GBS patients receiving a single dose of ANX005 (75 mg/kg) together with IVIg (2 g/kg over 5 days).

Results Fourteen patients (median age = 41 years) with baseline GBS-disability scale (DS) of 3-5 and Medical Research Council sum score (MRC) 0-42 were enrolled. Baseline sNfL ranged from 12 to 3,445 pg/ml. Combination ANX005 and IVIg demonstrated full C1q target engagement for 1-3 weeks. In 8 patients, 3 from Denmark and 5 from Bangladesh, with baseline MRC >20 and/or sNfL ≤652 pg/ml, early (≤3 weeks) functional improvement resulted in GBS-DS of 0 (37.5%), 1 (37.5%), and 2 (25.0%) at Week 26. In contrast, 6 Bangladeshi patients with baseline MRC ≤20 and/or sNfL >928 pg/ml showed delayed (≥4 weeks after admission) improvement and achieved a GBS-DS score of 3 or 4 at study completion. Baseline sNfL significantly correlated with the patient’s ability to improve [Spearman r = 0.63, 95% CI (0.13, 0.87)].

Conclusions ANX005 with IVIg was well tolerated and demonstrated robust target engagement. For the intended use, dose adjustment is not needed. Considering baseline prognostic factors, patients responded similarly to treatment, irrespective of geographic location. A longitudinal proportional odds efficacy analysis that fully captures patient trajectories over time is proposed for future studies. A phase 2/3 trial of ANX005 is ongoing in Bangladesh.

Authors/Disclosures
Henk-Andre A. Kroon, MD, MBA (Annexon Biosciences) PRESENTER	Dr. Kroon has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Kroon has stock in Annexon Biosciences.
	No disclosure on file
Zhahirul Islam	No disclosure on file
Nowshin Papri	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Eric Humphriss	No disclosure on file
	No disclosure on file
Sanjay C. Keswani, MBBS (Annexon BioSciences)	Dr. Keswani has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Keswani has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Nura Bio. Dr. Keswani has received stock or an ownership interest from Annexon Biosciences. Dr. Keswani has received stock or an ownership interest from Nura Bio.
	No disclosure on file
	No disclosure on file
Quazi Deen Mohammad, MD (National Institute of Neuroscience (NINS).)	Dr. Deen Mohammad has nothing to disclose.