ANX005 for treatment of Guillain-Barré syndrome

Treatment with the investigational therapy ANX005 (Annexon, Brisbane, CA) was associated with faster and greater improvements in muscle strength and disability for people with Guillain-Barré syndrome compared with standard therapies such as intravenous immunoglobulin (IVIg) or plasma exchange (PE). The positive findings result from a matched patient cohort study that included participants from a previous phase 3 clinical trial and the real-world International Guillain-Barré Syndrome Outcomes Study (IGOS) registry. ANX005 is designed to block the complement component 1q (C1q) to reduce inflammation and nerve damage.

The study assessed 79 participants with Guillain-Barré syndrome from Bangladesh and the Philippines who received treatment with ANX005 30 mg/kg who were matched with 79 participants from the IGOS registry who received standard care with IVIg or PE.At week 1, individuals who received ANX005 treatment demonstrated an improvement of >10 points in Medical Research Council (MRC) muscle strength sum-scores compared with those receiving IVIg/PE (P<.0001).

At week 8 (the primary endpoint for the phase 3 trial), people treated with ANX005 were approximately 2 times as likely to be in a better state of health than those who received IVIg/PE (P=.0459) according to scores on the Guillain-Barré Syndrome–Disability Scale (GBS-DS).

Of the 79 participants who received ANX005, 15 required mechanical ventilation compared with 32 of the 79 participants who received IVIg/PE (P=.022).

Participants who received ANX005 spent a median of 12 fewer days in the ICU and on mechanical ventilation than those who received IVIg/PE.

“In this analysis, patients treated with a single dose of ANX005 showed improved and more rapid benefit on muscle strength and disability over matched patients treated with multiple days of IVIg or PE,” said Hugh Willison, MBBS, PhD, Professor Emeritus of Neurology a thte University of Glasgow and member of the IGOS Steering Committee. “Recognizing the common role of complement biology in GBS pathogenesis, it’s reasonable to expect these results could translate well to a broad population of patients with GBS.”

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Rajabally YA. Immunoglobulin and Monoclonal Antibody Therapies in Guillain-Barré Syndrome. Neurotherapeutics. 2022 Apr;19(3):885-896. doi: 10.1007/s13311-022-01253-4. Epub 2022 Jun 1. PMID: 35648286; PMCID: PMC9159039.

Abstract

Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy affecting 1-2 subjects per 100,000 every year worldwide. It causes, in its classic form, symmetric weakness in the proximal and distal limb muscles with common involvement of the cranial nerves, particularly facial weakness. Respiratory function is compromised in a case in four. Randomised controlled trials have demonstrated the benefit of therapeutic plasma exchange in hastening time to recovery. Intravenous immunoglobulin was subsequently shown to be as efficacious as plasma exchange in adult subjects. In children, few trials have shown the benefit of intravenous immunoglobulin versus supportive care. Pharmacokinetic studies suggested a relationship between increase in immunoglobulin G level post-infusion and outcome, implying administration of larger doses may be beneficial in subjects with poor prognosis. However, a subsequent trial of a second dose of immunoglobulin in such subjects failed to show improved outcome, while demonstrating a higher risk of thromboembolic side-effects. Monoclonal antibody therapy has more recently been investigated for GBS, after multiple studies in animal models, with different agents and variable postulated mechanisms of action. Eculizumab, a humanised monoclonal antibody against the complement protein C5, was tested in in two randomised, double-blind, placebo-controlled phase 2 trials. Neither showed benefit versus immunoglobulins alone on disability level at 4 weeks, although one study importantly suggested possible, clinically highly relevant, late effects on normalising function. A phase 3 trial is in progress. Preliminary results of a placebo-controlled ongoing study of ANX005, a humanised recombinant antibody against C1q inhibiting the complement cascade, have been promising.