Tanruprubart Shows Rapid Responses in First FORWARD Cohort for Guillain-Barre Syndrome

Annexon reported early results from the first 10 US and European patients treated with tanruprubart in its ongoing, open-label FORWARD study for Guillain-Barré syndrome (GBS).¹ Overall, all patients showed rapid, clinically meaningful improvement in muscle strength within 4 days of a single 30 mg/kg infusion, with the company describing the outcomes as consistent with previously reported phase 3 and real-world evidence findings.¹

“The early and marked improvements in this initial data from FORWARD are consistent with our Phase 3 and Real World Evidence findings,” Douglas Love, president and chief executive officer of Annexon, said in a statement.¹ “That consistency continues to strengthen the significant functional outcomes being achieved with our differentiated C1q-focused approach targeting neuroinflammation at its source.”

About the FORWARD study

FORWARD is an open-label study designed to give physicians and patients in the US and Europe direct experience with tanruprubart, including in pediatric patients, with the broader goal of supporting a wide intended label. The trial is tracking pharmacokinetics, pharmacodynamics, early effects on function and biomarkers, and safety in adult and pediatric patients with GBS. It is not a randomized or placebo-controlled study; its purpose is closer to a bridging or confirmatory-experience program than a traditional efficacy trial.

Early cohort findings

The first reported cohort included both male and female patients ranging from 12 to 78 years old and covering the spectrum of disease from moderate to severe. Four patients who were bedbound early in their disease course walked with or without assistance between days 2 and 8, and the 1 patient who required mechanical ventilation early in the disease course came off the ventilator within 4 days. The remaining 5 patients all showed marked gains in function within 48 hours.

“The early results from the FORWARD study are some of the most encouraging we have seen in GBS research and reinforce the potential of tanruprubart as a transformative treatment," Rafid Mustafa, MD, associate professor of neurology and vice chair for quality in the Department of Neurology at Mayo Clinic, said in a statement.¹

Annexon noted these early responses line up with what was seen in its pivotal phase 3 trial, where roughly 90% of patients demonstrated rapid, clinically meaningful improvement by day 8 of treatment.¹ Tanruprubart was generally well tolerated in the FORWARD cohort, with adverse events largely attributed to GBS itself or its complications rather than the drug, consistent with the phase 3 safety profile.¹

Thomas Harbo, MD, PhD, professor of neurology at Aarhus University and consultant neurologist at Aarhus University Hospital in Denmark, added that the speed of responses was "striking," noting that patients "who may have otherwise faced an uncertain road to recovery showed remarkable improvements in strength within days.”

Prior phase 3 and real-world evidence

The pivotal phase 3 trial (NCT04701164) randomized 241 patients with GBS aged 16 and older to a single IV infusion of tanruprubart at 30 mg/kg, 75 mg/kg, or placebo.² Data on quality-of-life outcomes, presented at the 2025 Peripheral Nerve Society Annual Meeting, showed that the 30 mg/kg group, the same dose used in FORWARD, had significant improvement on the EQ visual analog scale by week 1 (P = .0089), sustained through week 8 (P = .0391).^2,3 That group also showed significant gains on EQ-5D-5L domains including mobility, self-care, and usual activity by week 1 (all P < .0001), along with a 20% improvement in country-standardized index score after 1 week (P < .0001).³

Beyond the randomized trial, Annexon's EMA submission drew on a broader generalizability package intended to demonstrate that tanruprubart's effect extends beyond the Southeast Asian populations most heavily represented in earlier GBS trials. This included a large US and Southeast Asian biomarker dataset, a population pharmacokinetic analysis spanning US, EU, and Southeast Asian studies, and a roughly 2,000-patient real-world evidence study that matched tanruprubart-treated patients against those receiving IVIg or plasma exchange.²

Mechanism and regulatory path

Tanruprubart is a first-in-class monoclonal antibody designed to rapidly block C1q, the initiating molecule of the classical complement pathway, to stop complement-driven neuroinflammation and nerve damage in the peripheral and central nervous systems. To date, it has received Fast Track and Orphan Drug designations from the FDA and orphan drug designation from the EMA.¹

Annexon submitted its MAA to the EMA in January 2026, and the application remains under review. The company said FORWARD data are expected to support a planned BLA submission to the FDA, targeted for the fourth quarter of 2026.^1,2

Disease burden and unmet need

GBS is the leading cause of acute paralytic neuropathy worldwide, with no disease-modifying therapy currently approved in the US, resulting in more than 22,000 hospitalizations annually across the US and Europe and an estimated $20 billion in annual US healthcare costs.^1,4 Standard-of-care IVIg, itself not FDA-approved for GBS, provides incomplete benefit for many patients and performs comparably to plasma exchange rather than offering a clearly superior option; Annexon has cited mortality rates of up to 10% with standard care, and roughly 1 in 4 IVIg-treated patients still require ventilatory support.

REFERENCES
1. Annexon Reports First U.S. and European Patient Cohort of GBS FORWARD Study Demonstrated Rapid, Positive Clinical Responses in All Tanruprubart Treated Patients Within One Week. News release. Annexon, Inc. August 6, 2026. Accessed August 10, 2026. https://ir.annexonbio.com/news-releases/news-release-details/annexon-reports-first-us-and-european-patient-cohort-gbs-forward
2. Annexon Submits Tanruprubart Marketing Authorization Application to the European Medicines Agency for Guillain-Barré Syndrome. News release. Annexon, Inc. January 8, 2026. Accessed August 10, 2026. https://finance.yahoo.com/news/annexon-submits-tanruprubart-marketing-authorization-130000056.html
3. Morrison G, Lin P, Mohammad QD, et al. ANX005 improves health-related quality of life in patients with GBS compared to placebo. Presented at: 2025 Peripheral Nerve Society Annual Meeting; May 17-20, 2025; Edinburgh, Scotland. Abstract P338.
4. Uddin MI, et al. Plasma exchange (PE) versus intravenous immunoglobulin (IVIG) for the treatment of Guillain-Barré syndrome (GBS) in patients with severe symptoms: A systematic review and meta-analysis. Heliyon. 2023;9(3):e14126. doi:10.1016/j.heliyon.2023.e14126. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242495/