Sanofi and Denali’s ALS Candidate SAR443820 Fails Phase 2 Trial

The Phase 2 HIMALAYA trial, which evaluated SAR443820 (alternatively known as DNL788), a RIPK1 inhibitor developed by Sanofi and Denali Therapeutics for the treatment of amyotrophic lateral sclerosis (ALS), did not meet its primary endpoint of change in the ALSFRS-R clinical scale. Despite not releasing detailed safety and efficacy results, missing the primary endpoint was a significant blow to the collaboration, which also includes a multiple sclerosis (MS) study with the same drug, currently in Phase 2.

Sanofi and Denali Therapeutics initiated their partnership in 2018, with the goal of developing treatments for neurological and inflammatory diseases, including ALS and MS. The setback raises questions about the future of the ALS drug development under this collaboration.

- The HIMALAYA trial randomized 305 ALS patients to receive SAR443820 or placebo.
- This drug was part of a larger RIPK1 collaboration, which has faced setbacks in the past.
- Sanofi is currently testing SAR443820 in a Phase 2 multiple sclerosis trial, with a primary completion date set for September 2025.
- Denali is also pursuing another ALS candidate, DNL343, in a separate study.
- Denali's shares declined over 6% on the news of the Phase 2 trial failure.