The latest phase 3 trial of zuranolone, conducted by Sage Therapeutics and Biogen, involved 440 patients with major depressive disorder (MDD) and demonstrated a statistically significant reduction in depression symptoms at three days. This study, named CORAL, achieved its primary objective by showing a two-point reduction on the HMAD-17 scale. However, the durability of zuranolone's effects remains in question, as improvements over placebo were only a trend at 15 days and equivalent to control after 42 days.
This follows a pattern observed in previous trials, including the WATERFALL study, which also showed a strong initial response that narrowed over time. Despite these challenges, both companies view the results positively and plan to submit a rolling marketing application for zuranolone, aiming for completion in the second half of the year.
Zuranolone's rapid onset of action, significantly faster than traditional antidepressants, has fueled optimistic sales projections. Its potential to quickly alleviate severe depression symptoms, especially in patients at risk of self-harm or suicide, underscores its therapeutic promise. However, the drug's short window of efficacy raises questions about its commercial success and ability to meet blockbuster sales expectations.
Analysts are divided on zuranolone's market potential. While some believe the drug will likely gain approval, they note that stronger data would be beneficial to persuade physicians to alter their treatment approaches for MDD. Others anticipate a contentious FDA review process, citing the drug's modest efficacy and durability concerns.
Sage Therapeutics already markets Zulresso (brexanolone) for postpartum depression, but with limited sales. The company is looking to zuranolone for significant growth, despite the uncertainties surrounding its commercial viability.
