Sanofi and Denali’s ALS therapy misses preliminary endpoint in Phase II trials

Sanofi and Denali Therapeutics' ALS therapy, SAR443820/DNL788, didn't meet its primary endpoint in the Phase II HIMALAYA trial. The trial aimed to gauge its effect on the ALS Functional Rating Scale-Revised (ALSFRS-R), vital for assessing disease severity and functional ability in ALS.

ALS, a rare, fatal motor neuron disease, leads to progressive nerve cell degeneration in the spinal cord and brain, affecting approximately 2 in 100,000 individuals yearly.

Despite the setback, Sanofi is exploring SAR443820/DNL788's potential for multiple sclerosis (MS) treatment in a Phase II trial (NCT05630547), expected to conclude in 2025.

Sanofi acquired SAR443820/DNL788 through a $1 billion licensing deal with Denali, aiming to target the RIPK1 pathway linked to inflammation and cell death. However, the collaboration faced challenges.

In October 2023, Sanofi halted the Phase II trial (NCT04781816) for its RIPK1 inhibitor, eclitasertib, in patients with cutaneous lupus erythematosus (CLE). They redirected resources to develop DNL788 after pausing DNL747 trials for Alzheimer’s disease and ALS in June 2020.