The TREM2 stabilizer failed to show efficacy in a Phase 2 trial of patients with early-stage 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.
Novartis—and the amyotrophic lateral sclerosis community—have suffered another tough break. The Swiss pharma has halted development of a TREM2 stabilizer for the neurodegenerative disease, marking a fourth clinical blow for the company in less than a month.
The decision to discontinue development of VHB937, also known as lifonebart, in ALS comes after the asset failed to meet either the primary or secondary endpoints in the Phase 2 ASTRALS trial of patients with early-stage disease.
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), a scale measuring limb, respiratory and bulbar function, per a U.S. government database. The trial page was last updated July 7 and is still listed as “active, not recruiting.”
Secondary endpoints involved decline in respiratory function and levels of neurofilament light (NfL), a known biomarker of neurodegeneration.
The news of the program’s discontinuation was revealed in a letter to the European Organization for Professionals and People with ALS, dated Aug. 25. Novartis confirmed the news in an email to BioSpace Wednesday morning.
Detailed trial results will be shared in an oral presentation at the 37th International Symposium on ALS/MND in December.
For Novartis, this development marks the fourth asset stumble in less than a month. On Sept. 4, the company revealed that its Lp(a)-targeting antisense therapy pelacarsen failed to show significant benefit on cardiovascular risk in a Phase 3 study—throwing the whole target into question, according to some analysts. Then, the pharma’s antibody oligonucleotide conjugate del-desiran—a cornerstone of Novartis’ $12B pick up of Avidity BioSciences last year—failed a Phase 3 trial in myotonic dystrophy type 1.
These announcements all followed the news that Novartis had suspended multiple immunology and neurology studies following three deaths among patients receiving its investigational CAR T therapy rapcabtagene autoleucel. Novartis’ shares fell 13% last week and the pharma’s board is facing scrutiny about the R&D fails and overall M&A strategy.
Needless to say, Novartis is not having a good month, nor is the ALS community. On Tuesday, Axoltis Pharma reported another miss in the indication for NX210c—a cyclic peptide of 12 amino acids—being evaluated in a mid-stage study.
While NX210c did not meet the trial’s Phase 2 primary endpoint of change from baseline to week 6 in NfL or ratio of albumin concentration in cerebrospinal fluid, “consistent positive trends were observed in secondary and exploratory assessed parameters,” according to Axoltis. Post-hoc analysis showed “substantial reduction in ALSFRS-R decline rate versus placebo at week 6,” a benefit that was sustained at a four-month follow-up.
These signals are enough to support the drug’s continued development in ALS, Annette Janus, the company’s chief medical officer, said in a prepared statement.
