Novartis has extended its losing streak, stopping an amyotrophic lateral sclerosis (ALS) program after flunking a phase 2 trial.
The study compared VHB937, a TREM2 stabilizer and activator, to placebo in 251 people with early-stage ALS. Evidence that TREM2 plays a crucial role in neurodegeneration has fueled interest in targeting the protein to treat conditions including ALS and Alzheimer’s disease. In theory, activating TREM2 can make microglia, a type of immune cell, protect motor neurons and improve patient outcomes.
Novartis’ Astrals trial failed to validate the theory. The study missed its primary and secondary endpoints, a Novartis spokesperson said via email, confirming an update from the nonprofit MND Association.
The drugmaker responded to the setback by discontinuing development of VHB937 in ALS. A phase 2 trial of the drug candidate, which is also called lifonebart, continues to enroll Alzheimer’s patients. Target validation for TREM2 is stronger in Alzheimer’s than ALS, Guggenheim Securities analysts said in a June note about a conversation with Fiona Marshall, Ph.D., president of biomedical research at Novartis.
Novartis’ ALS setback adds to the poor record of TREM2 drug candidates in the clinic. In 2024, a phase 2 trial of Alector’s AbbVie-partnered TREM2 activator in Alzheimer’s missed its primary endpoint. Last year, Vigil Neuroscience reported the failure of its TREM2-activating antibody, although the biotech still managed to sell its small-molecule agonist of the target to Sanofi.
While history suggested the ALS trial was a risky bet, Novartis needed a win after a tough few weeks for its R&D team. In quick succession, Novartis paused autoimmune CAR-T trials in response to three deaths and reported the failures of key studies of an Lp(a)-lowering drug and a muscle-wasting disease therapy. Novartis’ only respite was a win for Rhapsido in multiple sclerosis.
The setbacks raised questions about Novartis’ M&A strategy and, by weakening the prospects of mid- to long-term growth drivers, potentially intensified its need to strike deals. On Wednesday, Novartis bolted on technology to enhance its neuroscience R&D group, agreeing to pay Sironax $125 million for a brain delivery platform. The platform could help Novartis get large molecules to targets in the brain.