Abstract Details

Title Early Targeted C1q Inhibition With Tanruprubart Improves Functional Recovery in Guillain-Barré Syndrome: Results From a Phase Three Study

Topic Neuro Trauma and Critical Care

Presentation(s) S21 - Neurocritical Care (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Objective Determine whether C1q inhibition with tanruprubart improves functional recovery in Guillain-Barré syndrome (GBS), and whether effects are amplified with earlier treatment or in patients with limited axonal damage (consistent with motor forms of GBS).

Background Early diagnosis and treatment are critical in GBS, as complement-mediated nerve inflammation and injury progress rapidly during the acute phase. C1q activation initiates this cascade. The extent of neuroinflammation and nerve damage at treatment initiation determines the speed and range of functional recovery. Tanruprubart, a monoclonal antibody that selectively and rapidly inhibits C1q, has demonstrated early improvement in muscle strength and disability in patients with GBS.

Design/Methods This phase 3, double-blind, placebo-controlled study (NCT04701164) evaluated 242 patients with GBS, aged ≥16 years with GBS disability score (GBS-DS) 3–5, randomized to a single IV infusion of tanruprubart (30 or 75 mg/kg) or placebo (not receiving IVIg or plasma exchange). Patients were treated within 10 days of weakness onset. Treatment effects on GBS-DS at Week 8 were evaluated by time from onset of weakness to dosing and baseline neurofilament light (NfL), a biomarker of axonal damage.

Results Overall, tanruprubart 30 mg/kg treatment showed an adjusted common odds ratio (aOR) for GBS-DS improvement at Week 8 of 2.4 compared to placebo (95% CI: 1.29–4.50; p=0.0058). Benefit was greater with treatment started ≤5 days from onset of weakness vs >5 days (aOR 3.4, 95% CI: 1.17–10.46, p=0.031) or when baseline serum NfL was <115 pg/mL vs ≥115 pg/mL (≤40% percentile; aOR 3.9, 95% CI: 1.55–10.14, p=0.005).

Conclusions Patients diagnosed and treated early in the disease course (≤5 days from onset), or with limited axonal damage (low baseline NfL), achieved greater functional improvement (GBS-DS). These results support the pivotal role of classical complement activation in GBS, highlight the need for rapid diagnosis, and the benefit of early targeted C1q inhibition.

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.
Zhahirul Islam	Zhahirul Islam has nothing to disclose.
Jose C. Navarro, MD	Dr. Navarro has nothing to disclose.
Khan Abul Kalam Azad, MD, MBBS, MACP, FRCP	Prof. Azad has nothing to disclose.
Glenn Morrison, PhD (Annexon Biosciences)	Dr. Morrison has received personal compensation for serving as an employee of Alector. Dr. Morrison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG . Dr. Morrison has stock in Alector. Dr. Morrison has received intellectual property interests from a discovery or technology relating to health care.
Erik Pulkstenis, PhD	Dr. Pulkstenis has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Pulkstenis has stock in Annexon Biosciences. Dr. Pulkstenis has stock in AbbVie.
Quazi Deen Mohammad, MD (National Institute of Neuroscience (NINS).)	Dr. Deen Mohammad has nothing to disclose.

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