Vigil Neuroscience Provides Update on Iluzanebart Phase 2 IGNITE Trial in ALSP
- Drug demonstrated favorable safety, tolerability and pharmacokinetic profile
- Research contributed to increased awareness and understanding of ALSP disease
- Phase 2 IGNITE trial showed no beneficial effects on biomarker or clinical efficacy endpoints
- Company is discontinuing the Phase 2 long-term extension study
- Major setback for company's lead drug candidate
Insights
Vigil Neuroscience's lead drug iluzanebart failed Phase 2 ALSP trial with no clinical benefit, prompting program discontinuation.
The announcement from Vigil Neuroscience represents a significant setback for their lead program targeting ALSP (adult-onset leukoencephalopathy with axonal spheroids and pigmented glia), a rare neurodegenerative disease. While iluzanebart demonstrated favorable safety and tolerability at both 20 mg/kg and 40 mg/kg doses, the critical finding is the complete absence of beneficial effects on both biomarker and clinical efficacy endpoints.
This is particularly concerning as TREM2 agonism via iluzanebart (a monoclonal antibody) was Vigil's core therapeutic approach. The company's decision to discontinue the long-term extension study signals the effective termination of this development program. For rare disease therapeutics, Phase 2 failures typically indicate fundamental issues with the mechanism of action or target selection.
The language in the press release - referring to "not the data outcome we hoped to see" - employs standard corporate understatement for what appears to be a comprehensive clinical failure. With no partial signals of efficacy mentioned, this suggests the TREM2 pathway may not be viable for ALSP treatment as originally hypothesized. The termination of their lead program will likely force a significant strategic reassessment for Vigil, whose pipeline and scientific platform were substantially focused on this approach and indication.
WATERTOWN, Mass., June 04, 2025 (GLOBE NEWSWIRE) -- Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotechnology company committed to harnessing the power of microglia for the treatment of neurodegenerative diseases, today announced an update on the Phase 2 IGNITE open-label clinical trial evaluating iluzanebart, a monoclonal antibody TREM2 agonist, for the potential treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).
Iluzanebart demonstrated a favorable safety, tolerability and pharmacokinetic profile across both the 20 mg/kg and 40 mg/kg dose cohorts. The Phase 2 IGNITE trial showed no beneficial effects on biomarker or clinical efficacy endpoints with treatment of iluzanebart in ALSP patients. Based upon these results, the Phase 2 long-term extension study is being discontinued in accordance with the process previously disclosed.
“We have worked diligently over the past five years advancing our ALSP program in pursuit of a potentially effective therapy for this devastating neurodegenerative disease. Through every step, we have been deeply inspired by and profoundly grateful for the ALSP community, including patients and their families, patient advocacy groups, physicians, and trial investigators, whose courage, commitment, and partnership have been essential to driving this work forward,” said Ivana Magovčević-Liebisch, Ph.D., J.D., President and Chief Executive Officer of Vigil. “While this is not the data outcome we hoped to see for our iluzanebart program and our patients, I am proud of what we have accomplished together. We believe our efforts and the data collected from the IGNITE clinical trial and ILLUMINATE natural history study have increased awareness and provided a deeper understanding of ALSP.”
About the Phase 2 IGNITE Clinical Trial and ILLUMINATE Natural History Study
IGNITE was a global Phase 2, open-label proof-of-concept trial designed to evaluate iluzanebart in 20 patients with symptomatic ALSP who have a confirmed CSF1R gene mutation. The primary objective of the IGNITE trial was to evaluate the safety and tolerability of iluzanebart. Secondary outcome measures included the evaluation the effects of iluzanebart on target engagement and on MRI and NfL biomarkers of disease progression. Exploratory outcome assessments included the evaluation of clinical efficacy measures using standard cognitive, motor and functional assessments of iluzanebart in patients with ALSP. Patients enrolled in the trial received an intravenous (IV) infusion of iluzanebart at 20 mg/kg or 40 mg/kg approximately every four weeks for a treatment duration of one year. ILLUMINATE is a prospective, multi-center, natural history study of patients with ALSP and a confirmed CSF1R gene mutation. It is the first natural history study in ALSP and was designed to better understand the disease and help inform the clinical development of iluzanebart.
About ALSP
ALSP is a rare, inherited, autosomal dominant neurological disease with high penetrance. It is caused by a mutation to the CSF1R gene and affects an estimated 19,000 people in the United States, with similar prevalence in Europe and Japan. The disease generally presents in adults in their forties, is diagnosed through genetic testing and established clinical/radiologic criteria and is characterized by cognitive dysfunction, neuropsychiatric symptoms, and motor impairment. These symptoms typically exhibit rapid progression with a life expectancy of approximately six to seven years on average after diagnosis, causing significant patient and caregiver burden. There are currently no approved therapies for the treatment of ALSP, underscoring the high unmet need in this rare indication.
About Vigil Neuroscience
Vigil Neuroscience is a clinical-stage biotechnology company focused on developing treatments for both rare and common neurodegenerative diseases by restoring the vigilance of microglia, the sentinel immune cells of the brain. Vigil is utilizing the tools of modern neuroscience drug development across multiple therapeutic modalities in its efforts to develop precision-based therapies to improve the lives of patients and their families. Vigil is developing VG-3927, a novel small molecule TREM2 agonist, to treat common neurodegenerative diseases associated with microglial dysfunction, with an initial focus on Alzheimer’s disease (AD).
Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements” of Vigil Neuroscience (“Vigil” or the “Company”) that are made pursuant to the safe harbor provisions of the federal securities laws, including, without limitation, express or implied statements regarding: the potential therapeutic benefit of the Company’s product candidates, including iluzanebart and VG-3927; the Phase 2 IGNITE clinical trial including the future release of data and the Company’s plan to discontinue the Phase 2 IGNITE trial; beliefs about observations made analyzing clinical trial data to date, including with respect to iluzanebart . Forward-looking statements are based on Vigil’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties inherent in the development of product candidates, including the conduct of research activities and clinical trials; whether results from prior preclinical studies and clinical trials will be predictive of the results of subsequent preclinical studies and clinical trials; whether Vigil’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and the timing and content of additional regulatory information from the FDA; as well as the risks and uncertainties identified in the Company’s filings with the Securities and Exchange Commission (SEC), including Vigil’s Annual Report on Form 10-K for the year ended December 31, 2024, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, and any subsequent filings Vigil makes with the SEC. Forward-looking statements contained in this announcement are made as of this date, and Vigil undertakes no duty to update such information except as required under applicable law. Readers should not rely upon the information in this press release as current or accurate after its publication date.
Internet Posting of Information
Vigil Neuroscience routinely posts information that may be important to investors in the 'Investors' section of its website at https://www.vigilneuro.com. The company encourages investors and potential investors to consult our website regularly for important information about Vigil Neuroscience.
Investor Contact:
Leah Gibson
Vice President, Investor Relations & Corporate Communications
Vigil Neuroscience, Inc.
lgibson@vigilneuro.com
Media Contact:
Megan McGrath
CTD Comms, LLC
megan@ctdcomms.com
FAQ
What were the results of Vigil Neuroscience's (VIGL) Phase 2 IGNITE trial for iluzanebart?
Why is Vigil Neuroscience (VIGL) discontinuing the Phase 2 long-term extension study?
What is iluzanebart and what was it designed to treat?
What doses of iluzanebart were tested in the VIGL Phase 2 trial?
