What does this score mean?
The Confidence Index is an editorial methodology score indicating to what extent the scientific finding evaluated on this page can be trusted, not the success rate of the treatment. Study design, risk of bias, sample size, precision, direct applicability, reproducibility, transparency, and clinical relevance are evaluated together.
What did the study investigate?
It evaluated whether the TREM2-targeted VHB937/lifonebart treatment provided safety and efficacy in early-stage ALS.
How was it done?
The randomized, placebo-controlled Phase II ASTRALS study was conducted, enrolling 251 early-stage ALS patients worldwide.
What was found?
According to the company update, the primary and secondary endpoints were not met, and the ALS development program was discontinued. The negative result demonstrates that target biology does not automatically translate into clinical benefit.
Limitations of the study
Because the complete, detailed peer-reviewed results are not yet publicly available, interpretation regarding effect size, subgroups, and the reason for the failure remains limited.
What does it mean clinically?
This result does not support a clinical benefit of VHB937 in ALS; it also demonstrates the scientific value of negative randomized studies in ruling out therapeutic targets.
What do we not know yet?
To what extent dose, target engagement, disease stage, or biological heterogeneity contributed to the outcome, and the role of the TREM2 axis in other neurodegenerative diseases, remains unclear.
Source
Full citations and links to sources are preserved in the detailed evaluation section of this page.
Written and medically reviewed by: Dr. Kerem Çağlayan · All Scientific Research
Detailed evaluation
Clinical research evaluation · September 18, 2026
The TREM2 axis, which targets neuroinflammation, is being investigated in neurodegenerative diseases such as Alzheimer’s and ALS. Novartis’s VHB937 (lifonebart; VHB937B1) program yielded a significant negative result in ALS.
The ASTRALS study
The Phase II ASTRALS study enrolled 251 early-stage ALS patients worldwide. The study was designed as a randomized and placebo-controlled trial to evaluate the safety and efficacy of VHB937.
Result
According to the company’s update, the study did not meet its primary and secondary endpoints. Consequently, the development program for VHB937 in the ALS indication was discontinued.
Why are negative studies important?
Negative results are also critical scientific data that test target biology. TREM2 is associated with microglial immune response and inflammation; however, a biological target being meaningful does not mean it will translate into clinical benefit in every disease.
The reason for the failure in ALS cannot be finalized without detailed data disclosure. Dose, target engagement, disease heterogeneity, or timing of intervention are possible explanations.
Alzheimer’s program
A separate Phase II study with VHB937 in early Alzheimer’s disease is ongoing. The ALS result does not automatically determine the outcome of the Alzheimer’s study.
Quality of evidence
Negative clinical result in a randomized Phase II trial.
Sources
This content is a scientific evaluation of a clinical trial result.