Sanofi has stopped a phase 2 trial of Denali Therapeutics-partnered oditrasertib in multiple sclerosis. The French drugmaker tore the RIPK1 inhibitor trial from its list of active studies after it failed to meet its primary and secondary endpoints, dealing a further blow to a collaboration with a troubled history.
Denali picked up the RIPK1 program through the acquisition of Incro Pharmaceuticals in 2016 and flipped the assets to Sanofi two years later. Sanofi paid Denali $125 million upfront in the belief inhibiting the kinase may stop tissue damage and neuronal death by disrupting the production of cytokines and other proinflammatory factors. Across six years of effort, Sanofi has failed to validate the idea in the clinic.
News of the latest clinical setback emerged after the market closed Thursday, when Denali provided an update on the phase 2 multiple sclerosis trial in a brief financial filing. Sanofi has stopped the study after chalking up failures on the primary and key secondary endpoints.
The study was comparing the effect of oditrasertib, also known as SAR443820, and placebo on serum neurofilament levels. Neurofilament light chain (NfL) is a neurodegenerative disease biomarker. A drop in NfL could reflect a reduction in axonal damage or neuronal degeneration, events that cause the release of the biomarker. Oditrasertib failed to cause a positive change in NfL compared to placebo.
The failure wipes out another potential path forward for the RIPK1 inhibitor. Sanofi and Denali stopped development of their original lead candidate in 2020 in response to preclinical chronic toxicity studies. Oditrasertib took up the baton, only to fail a phase 2 amyotrophic lateral sclerosis trial in February and now swing and miss at multiple sclerosis.
Sanofi’s termination of the multiple sclerosis study means there are no active trials of oditrasertib. The RIPK1 collaboration continues through SAR443122, a peripherally restricted drug candidate that flunked a phase 2 test in cutaneous lupus erythematosus last year but is still in development in ulcerative colitis.
The ulcerative colitis trial, which is 13 months away from completion, is one of the last entries on the dwindling list of RIPK1 studies. GSK studied a candidate in several indications from 2015 to 2021. Boston Pharmaceuticals picked up a RIPK1 inhibitor from GSK in 2021, the same year that Eli Lilly paid Rigel Pharmaceuticals $125 million for a candidate that is now in a phase 2 rheumatoid arthritis trial.