Annexon (NASDAQ:ANNX) said it expanded its pivotal ARCHER II trial of vonaprument in geographic atrophy, adding an independent 24-month dual primary endpoint alongside the study’s existing 15-month primary endpoint. The company said it remains confident in a planned fourth-quarter assessment of the 15-month endpoint while seeking to capture longer-term efficacy data for a potential product label.
President and Chief Executive Officer Doug Love said the company’s two lead programs are approaching important regulatory and clinical milestones: tanruprubart in Guillain-Barré syndrome, or GBS, and vonaprument in geographic atrophy, or GA. Annexon also said it entered into a credit facility with Oxford Finance during the second quarter that provides access to up to $200 million in non-dilutive capital and extends its cash runway into 2028.
GBS Program Advances Toward Regulatory Filings
Jamie Dannenberg, Annexon’s executive vice president and chief medical officer, presented initial results from the first 10 patients in the FORWARD study, who each received a single 30 milligram-per-kilogram infusion of tanruprubart. According to the company, all 10 patients showed clinically meaningful improvement in muscle strength within four days of treatment.
- Four patients who were bed-bound regained the ability to walk with or without assistance between days two and eight.
- One patient who required mechanical ventilation was weaned from the ventilator within four days.
- Five additional patients showed marked functional improvement within 48 hours of treatment.
Dannenberg said the initial cohort included patients ranging from 12 to 78 years old and represented moderate-to-severe disease. Tanruprubart was generally well tolerated, with the most significant adverse events related to GBS and its expected complications, according to the company.
The results were consistent with Annexon’s prior Phase III findings, in which the company said about 90% of treated patients demonstrated rapid, clinically meaningful improvement by day eight. The FORWARD study is intended to broaden the company’s experience in U.S. and European patients, including pediatric patients, while assessing pharmacokinetics, pharmacodynamics, function, biomarkers and safety.
Annexon said GBS remains a serious neuromuscular emergency with no approved targeted therapies that meaningfully alter its course. Dannenberg said intravenous immunoglobulin, or IVIG, is the current standard of care but is not FDA-approved for GBS and may provide incomplete benefit for some patients.
ARCHER II Adds 24-Month Endpoint
In GA, Annexon enrolled 659 patients in ARCHER II, exceeding its original target by 30 patients. Lloyd Clark, senior vice president of ophthalmology strategy and innovation, said patient discontinuation has remained below 10% and dosing compliance has exceeded 95%, both better than the company’s targets.
All eligible participants have received at least 12 months of treatment, and masked event accrual remains in line with Annexon’s projections, Clark said. The company said the trial is powered at more than 90% at both the 15-month and 24-month time points.
The added 24-month endpoint will not change the ongoing masked conduct of the trial, which had already been designed to follow patients for 24 months. The company said the addition is intended to provide more time for vonaprument to demonstrate the growing treatment effect it observed in its proof-of-concept study.
An independent data monitoring committee is expected to assess the 15-month primary endpoint in the fourth quarter. If the committee determines that the 15-month endpoint has been met, Annexon expects to begin separate analyses of the trial’s two sub-studies, with results anticipated in the first quarter of 2027. Alternatively, the committee could recommend continuing through the 24-month analysis. Annexon expects the full ARCHER II study, including the 24-month analyses, to be completed in the third quarter of 2027.
Management told analysts that the company will remain blinded to patient-level data if the trial continues to the 24-month analysis. The company also said it has not disclosed the specific split of statistical alpha between the 15-month and 24-month endpoints, but maintained that the 15-month analysis remains well powered.
Focus on Vision Preservation
GA affects about 8 million people globally, including roughly 1.5 million in the United States, according to Annexon. Clark said currently approved treatments have not demonstrated preservation of visual acuity.
During the question-and-answer session, management said its central objective for vonaprument is preserving vision rather than solely slowing lesion growth. Love said Annexon expects to see protection of retinal pigment epithelium lesion growth over time, citing a 10% protection over a six-month period in the second half of the company’s earlier ARCHER study. However, management said it views photoreceptor and neuronal-cell protection, including measurement through the ellipsoid zone biomarker, as particularly important in the neurodegenerative disease.
Vonaprument has FDA Fast Track designation, while the European Medicines Agency has granted the program PRIME designation and selected it for its Product Development Coordinator pilot, Annexon said. The company also announced the initiation of an ARCHER II open-label extension study that will allow patients to receive vonaprument after month 24 and enable longer-term safety and benefit assessments.
Love said Annexon has also continued work on an oral small-molecule therapy designed to selectively inhibit the complement classical pathway, though no additional clinical or regulatory details were provided during the call.
About Annexon (NASDAQ:ANNX)
Annexon Inc is a clinical-stage biotechnology company focused on the discovery and development of complement-targeted therapies for patients with neurodegenerative and neuroimmune diseases. The company’s research platform centers on the inhibition of the C1 complex, a key initiator of the classical complement pathway implicated in several rare and life-threatening disorders. By selectively targeting upstream complement activation, Annexon aims to prevent the aberrant immune-mediated damage that characterizes conditions such as Guillain-Barré syndrome (GBS) and autoimmune neuropathies.
At the core of Annexon’s pipeline is ANX005, a humanized monoclonal antibody directed against the C1q subcomponent, currently in Phase 2 clinical trials for acute GBS and chronic neurodegenerative indications.
