Novartis halts ALS drug development after Phase 2 trial failure, extending R&D setbacks

Novartis has halted development of an investigational ALS drug candidate after it failed to meet its goals in a Phase 2 trial.

According to U.S. biotech publication Fierce Biotech on the 17th (local time), Novartis failed to meet either the primary or secondary endpoints in a Phase 2 trial comparing the TREM2 activator VHB937 with placebo in 251 patients with early-stage ALS.

A Novartis spokesperson confirmed the results by email and said the company would discontinue development of the compound for ALS. The statement is consistent with information from the nonprofit Motor Neurone Disease Association (MND Association).

TREM2 is a protein that plays a key role in neurodegeneration. The theory has been that activating it could enable microglia, immune cells, to protect motor neurons. This trial, however, did not validate that theory.

The compound is also known as liponevat, and a Phase 2 trial in patients with Alzheimer’s disease is ongoing. In a report last June, Guggenheim Securities analysts said the rationale for targeting TREM2 was stronger in Alzheimer’s disease than in ALS.

The failure adds to the disappointing clinical track record of TREM2 drugs. In 2024, a Phase 2 Alzheimer’s trial of a TREM2 activator co-developed by Alector and AbbVie failed to meet its primary endpoint, and last year Vigil Neuroscience reported the failure of a TREM2-activating antibody.

Novartis has recently faced a series of setbacks in research and development. It temporarily paused a trial of an autoimmune CAR T-cell therapy after three deaths, and key studies of a lipoprotein(a)-lowering drug and a treatment for muscle-wasting disease also failed. The multiple sclerosis drug Rhapsido was its only success.

The setbacks have raised questions about Novartis’ acquisition strategy and increased the need for deals to secure medium- and long-term growth drivers. Novartis said today it had agreed to pay Sironax $125 million to license a brain-delivery platform. The technology could help deliver large-molecule drugs to targets in the brain.