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News
A promising ALS drug hits a wall. The RIPK1 inhibitor SAR443820 failed to slow functional decline in the phase 2 HIMALAYA trial, showing no meaningful benefit over placebo while also racking up more adverse events and treatment discontinuations — largely due to elevated liver enzymes. The findings effectively close the door on further development of this compound for ALS.
A promising ALS drug hits a wall. The phase 2 HIMALAYA trial, published in The Lancet Neurology, tested SAR443820 (also known as DNL788) — an investigational RIPK1 inhibitor designed to target inflammatory signaling and cell death pathways implicated in ALS. Despite a solid biological rationale, the drug failed to deliver.
Over 24 weeks, functional decline (measured by the ALSFRS-R scale) was nearly identical between the SAR443820 and placebo groups, with a between-group difference of just −0.41 points — far from clinically meaningful. The drug group also saw more adverse events and a nearly three-times-higher discontinuation rate, driven mainly by elevated liver enzymes. The trial was ultimately terminated early.
By the Numbers:
Why it matters: ALS remains a devastating disease with very limited treatment options. While RIPK1 is still considered a biologically relevant target, this trial underscores how difficult it is to translate preclinical promise into real-world benefit — and signals that SAR443820 is unlikely to move forward for ALS.
