Novartis Halts ALS Drug After Phase 2 Failure, Deepening R&D Slump
Novartis has discontinued its amyotrophic lateral sclerosis (ALS) drug candidate VHB937 after a phase 2 trial failed to meet primary and secondary endpoints. The decision follows a series of recent clinical setbacks for the company, including failures in cardiovascular and muscle-wasting therapies, and prompts questions about its research strategy. While the ALS program is scrapped, development of the same drug for Alzheimer’s disease continues, as target validation remains stronger in that area. The company has also acquired a brain delivery platform from Sironax to bolster its neuroscience pipeline.
Key points
- Novartis stopped development of VHB937 (lifonebart) for ALS after the Astrals phase 2 trial missed its primary and secondary endpoints in 251 patients.
- The drug targets TREM2, a protein linked to neurodegeneration, with the theory that activating it helps microglia protect motor neurons.
- A phase 2 trial of VHB937 for Alzheimer’s disease is still enrolling patients, as analysts note stronger target validation for that condition compared to ALS.
- The ALS failure adds to a string of recent Novartis setbacks, including paused CAR-T trials, a failed Lp(a) cardiovascular drug, and a missed myotonic dystrophy trial.
- Novartis agreed to pay $125 million to Sironax for a brain delivery platform to enhance its neuroscience research capabilities.
Background
This development follows a turbulent period for Novartis’s R&D pipeline. In September 2026, the company reported that its pelacarsen drug failed to reduce cardiovascular events in a phase 3 trial, and its del-desiran therapy missed its primary endpoint in a myotonic dystrophy type 1 study, undermining the value of its $12 billion acquisition of Avidity Biosciences. Additionally, Novartis paused autoimmune CAR-T trials after three patient deaths. These consecutive failures have raised concerns about the company’s mid-to-long-term growth drivers and its acquisition strategy, prompting a renewed focus on securing new technologies like the Sironax platform to support future drug delivery.
Why it matters
The failure of VHB937 in ALS highlights the significant risks associated with targeting TREM2 in neurodegenerative diseases, following similar setbacks by Alector and Vigil Neuroscience. For Novartis, this setback compounds a series of high-profile clinical failures, potentially intensifying pressure on the company to succeed with its recent acquisitions and new technologies. The continued development of the drug for Alzheimer’s suggests that while the ALS hypothesis failed, the broader TREM2 target may still hold promise in other neurological conditions, influencing future investment and research directions in the sector.
What to watch
Novartis will continue enrolling patients in the phase 2 trial of VHB937 for Alzheimer’s disease, where target validation is considered stronger. The company will also integrate the newly acquired Sironax brain delivery platform into its neuroscience R&D group to improve the delivery of large molecules to the brain. Analysts will likely monitor Novartis’s ability to offset recent R&D losses with successful deals and new pipeline advancements, as the company seeks to stabilize its growth trajectory after a series of clinical setbacks.
- Novartis ends ALS program after phase 2 flop, adding to R&D woes Fierce Biotech
- Novartis’ TREM2 drug fails Phase 2 ALS trial Endpoints News
- Novartis Experimental Drug for ALS Fails in Another Pipeline Hit Bloomberg.com
- Novartis Suffers Another Setback After Stock-Rocking Failures Investor's Business Daily
- Novartis halts ALS drug development after mid-stage trial failure Reuters
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