Sanofi and Denali Therapeutics have announced that their investigational RIPK1 inhibitor, SAR443820 (also known as DNL788), failed to meet primary and secondary endpoints in a Phase 2 clinical trial for amyotrophic lateral sclerosis (ALS). The trial's disappointing results have led to the discontinuation of the drug's development for ALS.
The Phase 2 study evaluated the efficacy and safety of SAR443820 in patients with ALS. However, the drug did not demonstrate a statistically significant clinical benefit compared to placebo. Specific data regarding the magnitude of difference between the treatment and placebo arms were not disclosed in the initial announcement.
SAR443820 is a small molecule inhibitor of receptor-interacting protein kinase 1 (RIPK1), an enzyme involved in inflammation and cell death pathways. The rationale for targeting RIPK1 in ALS was based on preclinical evidence suggesting that RIPK1 inhibition could reduce neuroinflammation and neuronal damage, potentially slowing disease progression. Denali Therapeutics is continuing to evaluate SAR443820 in other indications.
ALS is a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately, respiratory failure. The disease affects approximately 30,000 people in the United States, with an estimated 5,000 new cases diagnosed each year. The median survival time after diagnosis is typically two to five years.
The current treatment landscape for ALS is limited. Riluzole and edaravone are the only FDA-approved drugs specifically for ALS, and they offer modest benefits in slowing disease progression. There remains a significant unmet medical need for more effective therapies that can significantly improve the quality of life and extend the survival of ALS patients. The failure of SAR443820 highlights the challenges and complexities of developing effective treatments for this devastating disease.
