Full Breakdown
Novartis Halts ALS Drug VHB937 After Mid-Stage Trial Failure
By Drooid · · How we work
Core Event: Termination of VHB937 Development
On September 16, Novartis AG announced that it is discontinuing development of VHB937 (also known as lifonebart), an experimental monoclonal antibody intended to treat amyotrophic lateral sclerosis (ALS). The decision follows a Phase 2 “ASTRALS” trial that did not demonstrate superiority over placebo on either the primary composite endpoint—survival without ventilator use combined with change on the ALS Functional Rating Scale-Revised (ALSFRS-R)—or on secondary measures such as respiratory decline and neurofilament light (NfL) levels.
Background & Context
VHB937 was designed to stabilize TREM2, a protein that modulates immune responses, inflammation, and waste clearance in the brain. Targeting TREM2 has been a focus for several biotech firms, yet recent mid-stage failures—including Alector’s 2024 ALS candidate—highlight the difficulty of translating this approach. The halt adds to a string of setbacks for Novartis this year: a late-stage heart-disease drug, a muscle-wasting therapy, and multiple CAR-T cell studies that were paused after three patient deaths.
Data & Statistics
- Enrollment: 251 participants with early-stage ALS (symptom onset <= 2 years) were enrolled, per clinicaltrials.gov.
- Primary Endpoint: Composite of ventilator-free survival and ALSFRS-R change; VHB937 did not meet this goal.
- Secondary Endpoints: Decline in respiratory function and NfL biomarker levels; both failed to show a statistically significant benefit.
- Trial Status: The trial page was last updated July 7 and remains listed as “active, not recruiting.”
Official Statements & Responses
Novartis confirmed the discontinuation in an emailed statement to Reuters, stating that the company is ending the VHB937 program after the Phase 2 results. The same communication noted that the trial’s detailed findings will be presented orally at the 37th International Symposium on ALS/MND in December. Following the announcement, Novartis’s U.S.-listed shares were marginally up.
Why It Matters
The failure underscores the broader challenge of delivering effective therapies for ALS, a rapidly progressive neurodegenerative disease with no cure. For Novartis, the setback intensifies scrutiny of its neuroscience pipeline, which already accounts for the smallest share of revenue among its four core therapeutic areas. In parallel, the company is investing in brain-delivery technology through a $125 million acquisition of Sironax’s platform, aiming to improve central-nervous-system access for future candidates.
Conflicting Reports & Gaps
Public disclosures have not included detailed efficacy numbers or safety data beyond the endpoint outcomes. The company plans to share more information at the December symposium, leaving a gap in the current public record regarding the magnitude of any observed trends.
Verbatim Quotes
- “In diseases like ALS, MS, where you need [central nervous system] access, you’re able to do that, so that’s very differentiating as well for us,” — Sironax CEO Shefali Agarwal
What’s Next
- December 2026: Novartis will present the full Phase 2 data at the International Symposium on ALS/MND.
- Brain-Delivery Platform: Following the acquisition, Sironax will retain rights to develop, manufacture, and commercialize select assets built on its “brain delivery modules,” potentially supporting future ALS, multiple sclerosis, and other neurodegenerative programs.
The cessation of VHB937 reflects both the scientific hurdles of targeting TREM2 in ALS and Novartis’s strategic shift toward leveraging novel delivery technologies to revive its neuroscience ambitions.