VHB937 Falls Short in ALS Trial
The ASTRALS study followed 251 people with early-stage ALS whose symptoms had started within the previous two years. Rather than looking at a single measure of physical decline, the trial assessed how long patients remained alive without permanent assisted ventilation alongside changes in their ability to carry out daily activities. The latter was tracked using the ALS Functional Rating Scale-Revised (ALSFRS-R). Researchers also examined other measures of disease progression, with VHB937 compared against a placebo.
Novartis said the study missed both endpoints, and it's pulling the plug on VHB937 for ALS as a result. The company hasn't released the actual numbers yet. Those will come in December, when Novartis presents the full ASTRALS data at the International Symposium on ALS/MND in Amsterdam.
TREM2 Strategy Faces Another Test
VHB937 was developed to stabilize and activate TREM2, a protein that helps regulate immune responses, inflammation and waste clearance in the brain. The approach is based on modifying microglial activity, with TREM2 being investigated as a target across neurodegenerative diseases.
It's not the first time a TREM2 drug has stumbled. Alector's TREM2 activator missed its primary endpoint in a Phase 2 Alzheimer's trial in 2024, while Vigil Neuroscience's TREM2-activating antibody failed the following year. Vigil's small-molecule TREM2 agonist, VG-3927, later became part of Sanofi's pipeline after the French drugmaker acquired Vigil in 2025.
Novartis is still testing VHB937 in Alzheimer’s disease, where a separate Phase 2 study is recruiting 407 participants. The trial is measuring changes in the Clinical Dementia Rating Scale-Sum of Boxes over 72 weeks, with a readout milestone set for 2029.
Pressure Builds on Novartis' Pipeline
The ALS failure comes after several other setbacks for Novartis in a short period. The company recently reported disappointing results for pelacarsen, an experimental cardiovascular drug, while its muscle-wasting treatment del-desiran failed a late-stage trial. Novartis also paused eight of 10 studies involving its rap-cel cell therapy after three patient deaths.
The sequence of setbacks has increased scrutiny of Novartis’ pipeline and its ability to generate new growth as older products face future patent expiries. Reuters reported that the company’s U.S.-listed shares were marginally higher after the ALS announcement, suggesting the result did not trigger a major immediate market reaction. For VHB937, the next meaningful test will come from its Alzheimer’s programme. The December release of the detailed ASTRALS results should also provide more information on why the ALS trial failed and whether the findings offer broader insight into the TREM2 approach.