Vigil's TREM2 Antibody Fails Phase II Trial, Sanofi Acquisition Unaffected

Vigil Neuroscience's monoclonal antibody iluzanebart has failed to meet its primary endpoints in a Phase II clinical trial for a rare brain disorder, prompting the discontinuation of its development. This setback comes just two weeks after Sanofi agreed to acquire Vigil for $470 million, though analysts suggest the trial results will not impact the pending acquisition.

Phase II Trial Results and Implications

The open-label proof-of-concept IGNITE trial, along with the concurrent ILLUMINATE natural history study, evaluated iluzanebart in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare progressive brain disease. Despite demonstrating favorable safety, tolerability, and pharmacokinetics, the antibody showed "no beneficial effects on biomarker or clinical efficacy endpoints," according to Vigil.

Ivana Magovčević-Liebisch, President and CEO of Vigil, expressed disappointment but emphasized the trial's contribution to ALSP awareness and understanding. The company will discontinue the long-term extension trial of iluzanebart as a result of these findings.

Impact on Sanofi Acquisition and Industry Landscape

The failure of iluzanebart is not expected to affect Sanofi's acquisition of Vigil, which was announced in late May. Notably, the buyout agreement did not include iluzanebart, which will be returned to its original licensor, Amgen. William Blair analysts stated they were "not surprised" by the results, citing previous questions about the drug's brain bioavailability and the interpretability of open-label study data in ALSP.

Sanofi's primary interest in the acquisition appears to be Vigil's other TREM2 agonist, VG-3927, which is being developed for neurodegenerative diseases such as Alzheimer's. The $470 million deal is still expected to close in the third quarter of 2025.

This setback for iluzanebart adds to recent challenges in the TREM2 space. In November 2024, Alector's TREM2 antibody failed a Phase II study for Alzheimer's disease, leading to layoffs at the company. These developments highlight the ongoing difficulties in developing effective treatments for neurodegenerative disorders.