Sanofi ends Denali-partnered MS trial after Phase 2 failure

Sanofi has announced the termination of a Phase 2 clinical trial investigating a drug from Denali for multiple sclerosis, effectively ending its development. According to Denali's SEC filing, Sanofi informed them that the drug, oditrasertib, did not achieve the primary or key secondary endpoints in the trial. Oditrasertib was designed to inhibit RIPK1, a signaling protein implicated in neuroinflammation and cell death, both of which are fundamental to diseases such as multiple sclerosis.

A representative from Sanofi confirmed that there are no other studies planned for oditrasertib. This development adds to a series of disappointing outcomes since the inception of the Sanofi-Denali collaboration. Initially, Sanofi made a significant investment in Denali by paying $125 million upfront in 2018, with more than $1 billion in potential milestone payments, emphasizing their high hopes for the RIPK1 target that oditrasertib was intended to hit.

Earlier this year, oditrasertib also failed a Phase 2 study for ALS, showing no improvement in patient symptoms as assessed by the ALS Functional Rating Scale. Another drug from the 2018 deal, DNL747, was discontinued in 2020 after Phase 1b data in Alzheimer's and ALS patients did not support further development.

Currently, a third drug from the collaboration, DNL758, is undergoing a Sanofi-led Phase 2 study in patients with ulcerative colitis. However, a previous study of this drug in patients with cutaneous lupus erythematosus was halted in October 2023 due to ineffectiveness.

Despite these setbacks, Denali remains financially stable. As of the end of June, the company reported $1.35 billion in cash, equivalents, and marketable securities, which will support the continued progression of its mid- to late-stage pipeline. This includes a promising treatment for Hunter syndrome, for which Denali plans to seek accelerated approval.

Last month, Denali announced a successful meeting with the FDA regarding a surrogate endpoint, with plans to submit an approval application in early 2025.