Novartis has revealed plans to pause development of Lifonebart (VHB937), an experimental monoclonal antibody drug targeting the TREM2 protein to treat neurodegenerative diseases. 

The news comes just days after the company announced its Phase III trial of antibody oligonucleotide conjugate (AOC) del-desiran had failed. 

VHB937 failed to show efficacy in the Phase II ASTRALS trial of patients with early-stage amyotrophic lateral sclerosis (ALS). This development follows two late-stage trial failures reported by Novartis last week, plus the news that the pharma has paused multiple CAR T cell trials following patient deaths. 

VHB937 did not meet either the primary or secondary endpoints in the clinical trial. The primary endpoint compared VHB937 to placebo using a composite score encompassing survival without the need for a ventilator and change on the ALS Functional Rating Scale–Revised (ALSFRS-R). 

Secondary endpoints involved decline in respiratory function and levels of neurofilament light (NfL), a known biomarker of neurodegeneration. 

Novartis says detailed trial results will be shared in an oral presentation at the 37th International Symposium on ALS/MND in December. 

This marks the fourth clinical trial setback for the company in a month. Early this month, Novartis placed holds on trials of its CAR-T therapy rapcabtagene autoleucel (rap-cel) after three study participants died due to a rare, potentially life-threatening inflammatory reaction. Then on 4 September, the company revealed that its Lp(a)-targeting antisense therapy pelacarsen failed to show significant benefit on cardiovascular risk in a Phase III study.  

Finally, on 8 September, Novartis announced that the global Phase III HARBOR study evaluating del-desiran in people living with myotonic dystrophy type 1 (DM1) did not demonstrate statistically significant improvement versus placebo. 

Del-desiran is one of three AOC therapies added to the Novartis neuromuscular pipeline through the acquisition of Avidity Biosciences.