FDA greenlights Vigil's phase 1 Alzheimer's trial, but not without a partial hold

Vigil Neuroscience has been granted clearance from the FDA to launch an early-stage Alzheimer’s trial, but that approval comes with strings attached: a partial clinical hold.

The FDA has approved Vigil’s investigational new drug (IND) application for VG-3927, a small molecule TREM2 agonist for Alzheimer’s in genetically defined subpopulations, the biotech said Friday after market close. The move allows Vigil to launch a phase 1 clinical trial in healthy volunteers, though the FDA implemented a partial clinical hold tied to the maximum exposure limit of VG-2927.

Vigil didn’t share what the limit cited by the FDA was but believes it is higher than the predicted efficacious dose of VG-3927, as based on preclinical models. The company plans to start dosing next month.

Based on initial comments from the regulatory agency, Vigil doesn’t think the partial hold was a result of any preclinical toxicology findings or TREM2 pharmacology, according to the Sept. 9 release. Such findings recently led to the discontinuation of Denali Therapeutics’ TREM2-targeting candidate DNL919. The Takeda-partnered asset was being assessed in a phase 1 trial that the FDA had placed a hold on after safety signals of moderate, reversible hematologic effects were observed at the highest dose.   

Vigil anticipates receiving further details from the FDA within the month regarding the hold. That being said, the neurodegenerative-focused biotech doesn’t believe the hold will impact its initial dosing abilities or create any delays in current clinical development plans for VG-3927.

Mizuho analysts said the IND approval and subsequent phase 1 launch is an “overall positive for the company,” per a Sept. 11 note.

“While the headline news of a PCH is likely to create some noise, given our understanding of the situation, we believe the PCH is very manageable, and hence we are not concerned about its potential impact on the development of this program,” the analysts wrote.

The analysts added that they believe Vigil is well-positioned, especially given its lead candidate VGL101, a fully human monoclonal antibody agonist for being assessed in a mid-stage study for patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. The rare microgliopathy condition currently does not have any approved treatments or even treatments in development.

Vigil plans to hold a virtual R&D event on Sept. 13 highlighting its small molecule TREM2 agonist program for Alzheimer’s.