Novartis ends ALS drug VHB937 after Phase 2 fail

Lab vials of an experimental ALS drug in a clinical research setting after Phase 2 trial failure VHB937

Key Points

01Novartis (NVS) has halted development of ALS drug VHB937 (lifonebart)
02Phase 2 ASTRALS trial did not meet primary or secondary endpoints
03VHB937 targets TREM2 through stabilizing or activating the protein
04The failure removes VHB937 from Novartis’ (NVS) neurology pipeline

Novartis drops ALS candidate VHB937 after Phase 2 setback

Novartis (NVS) has discontinued development of its experimental amyotrophic lateral sclerosis treatment VHB937, also known as lifonebart, following a failed Phase 2 trial. The decision comes after the ASTRALS study, which evaluated the drug in ALS patients, did not achieve its pre-specified primary or secondary endpoints. As a result, the asset is no longer being advanced in the company’s neurology development portfolio.

The ASTRALS trial was designed to assess whether VHB937 could provide clinical benefit in ALS, a progressive neurodegenerative disease with limited treatment options. While detailed numerical results have not been disclosed in the available reports, the lack of efficacy on both primary and secondary measures was sufficient for Novartis to end further development of the compound in this indication.

Details of the ASTRALS failure and mechanism of VHB937

VHB937 is characterized as a TREM2 stabilizer or activator, targeting the TREM2 protein that plays a role in microglial function in the central nervous system. The Phase 2 outcome indicates that modulating TREM2 with this particular molecule did not translate into meaningful clinical improvements for ALS patients within the parameters of the ASTRALS study.

The reports on the ASTRALS readout state that both primary and secondary endpoints were missed, but do not provide specific efficacy or safety data. No alternative development plans for VHB937 in ALS have been outlined in the information currently available. The compound’s removal from the neurology pipeline underscores the impact of the trial’s negative results on Novartis’ development strategy in this disease area.

Implications for Novartis’ ALS and neurology pipeline

The discontinuation of VHB937 represents a pipeline setback for Novartis in the ALS space, where successful late-stage programs remain limited across the industry. With VHB937 no longer in active development for ALS, the company’s neurology portfolio loses a TREM2-targeting candidate that had progressed into mid-stage clinical testing.

The failed ASTRALS trial highlights ongoing challenges in developing effective ALS therapies, even for mechanistically novel approaches. While the broader portfolio context is not detailed in the available material, the removal of VHB937 narrows Novartis’ current experimental options in this specific indication and reinforces the high attrition rates typical of neurodegenerative drug development.

Key Takeaways

01Novartis has removed VHB937 from its neurology development portfolio after the drug failed a key Phase 2 ALS trial, effectively halting development of this candidate in ALS.
02The ASTRALS study’s inability to meet primary and secondary endpoints shows that TREM2 modulation with VHB937 did not yield the intended clinical benefit in ALS.
03This outcome illustrates the persistent difficulty of advancing new ALS treatments through mid-stage trials and reduces Novartis’ near-term experimental options in the disease.

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