Sage Therapeutics and Biogen continue to push forward in depression and have new data they hope will impress investors and the FDA.
A phase III study of zuranolone met all of its key primary and secondary endpoints for the treatment of women with postpartum depression (PPD). The drug is also being developed to treat major depressive disorder (MDD).
According to the data, women treated with a 50 mg dose of zuranolone demonstrated a statistically significant and clinically significant improvement in depressive symptoms after two weeks, meeting the primary endpoint. The researchers compared changes from baseline to placebo, as measured by the 17-item total score of the Hamilton Depression Rating Scale (HAMD-17).
The mean HAMD-17 total score at day 15 for women who received zuranolone was -15.6 (0.82) versus -11.6 (0.82) for women who received placebo, reaching a difference -4.0 points. This occurred at a p-value of p=0.0007.
“The positive results from the SKYLARK study are a critical step in our mission to help women with postpartum depression find rapid relief from their depressive symptoms so they can regain a sense of who they are. said Barry Greene, CEO of Sage.
For secondary endpoints, the study saw improvement in depressive symptoms onset as early as day 3, which was maintained at all time points measured through day 45. Additionally, the study demonstrated improvement statistical significance of another key secondary endpoint: the change from baseline in the Clinical Global Impression Severity Scale at Day 15.
According to Sage, the company and Biogen have initiated an ongoing NDA submission for zuranolone in the treatment of major depressive disorder and expect to complete the filing in the second half of 2022. A related NDA submission for postpartum depression is scheduled for early 2023.
Despite the positive results touted by Sage, investors still have questions.
According to Jefferies’ Akash Tewari, while the data is strong overall, success was widely expected given their previous ROBIN study. Tewari wrote that questions remain about the overall market opportunity for PPD.
“We appreciate the clinical profile of SAGE’s lead candidate, zuranolone, for major depression; however, we believe investors should wait until the CORAL study is released and management communicates a clearer go-to-market strategy for ZRN before becoming bullish. In the long term, if zuranolone enters the market, we believe it has an attractive drug profile,” Tewari wrote.
Ultimately, the drug must be approved for MDD for it to have true commercial viability, Tewari said.
This isn’t the first time investors haven’t been completely sold on zuranolone. In 2021, when the first elements of phase III were published and the company was looking to recover from a phase III flop of its MOUNTAIN study, experts were not optimistic about the effect of zuranolone. Mizuho’s Vamil Divan said the Phase III -1.7 HAMD-17 mean baseline difference was not a clinically meaningful result, arguing that an investigational drug must show at least a three-point difference to do anything what kind of splash.
And while Sage’s stock price rose 10% on Wednesday, the company is still eyeing a 50% decline since that point last year.