Novartis Discontinues ALS Program After Lifonebart Misses Phase 2 Endpoints
- Novartis has discontinued development of lifonebart (VHB937), a TREM2 stabilizer/activator antibody, in amyotrophic lateral sclerosis (ALS).
- The decision follows Phase 2 ASTRALS trial results in which the drug missed both its primary and secondary endpoints.
- The study enrolled 251 patients with early-stage ALS; the primary endpoint was a composite of ventilator-free survival and change on the ALS Functional Rating Scale-Revised (ALSFRS-R), assessed at 40 weeks.
- The ALS discontinuation marks roughly the fourth pipeline setback for Novartis within about a month, part of a broader run of recent clinical disappointments.
- Lifonebart is not being abandoned entirely: Novartis continues to evaluate VHB937 in a separate, ongoing Phase 2 trial in early Alzheimer's disease.
Four pipeline setbacks in a month is a signal on Novartis's neuroscience screening bar, not just one bad trial. Either the Phase 2 go/no-go criteria were too generous or the underlying biology cases were weaker than the licensing rationale implied. On TREM2: one ALS miss doesn't kill the mechanism class — microglial-activation targets have had mixed reads across sponsors — but it does narrow the story to indication selection. The real tell is that Novartis kept the Alzheimer's Phase 2 running; that's management's actual vote on whether TREM2 biology holds, and it's the readout that will move the thesis. Watch for further neuro pruning next quarter, Alzheimer's data timing, and whether other TREM2-chasing biotech partners re-rate the target class.
Novartis ends ALS program after phase 2 flop, adding to R&D woes ↗