Novartis Halts ALS Drug VHB937 After Phase 2 Trial Misses All Endpoints

Key points

• Novartis ended development of VHB937 for ALS after the Phase 2 Astrals trial failed to validate the theory that activating TREM2 protects motor neurons.
• The trial included 251 participants with early-stage ALS and missed both primary and secondary endpoints, confirming reports from the MND Association.
• The drug candidate, also known as lifonebart, remains in a Phase 2 trial for Alzheimer’s disease, where TREM2 target validation is stronger.
• This failure follows recent setbacks for Novartis, including paused autoimmune CAR-T trials due to patient deaths and failed Phase 3 trials for Lp(a)-lowering and muscle-wasting disease therapies.
• Novartis recently acquired a brain delivery platform from Sironax for $125 million to enhance its neuroscience R&D capabilities.

Background

This development follows a series of significant R&D setbacks for Novartis in late 2026. In early September, the company reported that its Phase 3 trial for del-desiran, a treatment for myotonic dystrophy type 1, missed its primary endpoint, casting doubt on the value of its $12 billion acquisition of Avidity Biosciences. Shortly after, Novartis announced that pelacarsen, an Lp(a)-lowering drug, failed to reduce cardiovascular events in the Phase 3 Lp(a)Horizon trial despite significantly lowering the target protein. These consecutive failures have raised questions about the company's mid-to-long-term growth drivers and its acquisition strategy.

How outlets are covering it

Endpoints News reported that Novartis scrapped the ALS development program, noting the company is ending work on the candidate. Fierce Biotech provided additional detail, confirming that the Astrals trial missed both primary and secondary endpoints and highlighting that the failure adds to a poor record for TREM2 drug candidates, including recent misses by Alector and Vigil Neuroscience. Fierce Biotech also emphasized the broader context of Novartis' recent R&D woes, linking the ALS failure to other setbacks in autoimmune and cardiovascular trials, whereas Endpoints News focused primarily on the specific discontinuation of the ALS program.

Why it matters

The failure of VHB937 in ALS underscores the challenges of targeting TREM2 for neurodegenerative diseases beyond Alzheimer’s. For Novartis, this setback intensifies scrutiny on its R&D pipeline and acquisition strategy, particularly after recent failures in high-profile cardiovascular and neuromuscular trials. The decision to continue the Alzheimer’s program suggests that the company still sees potential in the TREM2 pathway for that specific indication, but the ALS failure may dampen investor confidence in the company's ability to deliver new growth drivers from its neuroscience portfolio.

What to watch

Novartis will continue enrolling patients in the Phase 2 trial of VHB937 for Alzheimer’s disease. The company is also integrating the brain delivery platform acquired from Sironax to potentially improve the delivery of large molecules to the brain. Analysts will likely monitor how Novartis addresses the recent string of R&D failures and whether it pursues further acquisitions to bolster its pipeline.