Sage Therapeutics terminated two long-suspended phase 3 zuranolone clinical trials after talks with the FDA led it to believe it can seek approval in major depressive disorder (MDD) without data from those studies. The biotech shared the update alongside news of a delay to data from another phase 3 because of slow enrollment during the pandemic.
Massachusetts-based Sage paused enrollment in its REDWOOD and RAINFOREST clinical trials in the fourth quarter of 2019 as part of the revision of its strategy in light of the failure of another study in MDD. At the time, Sage said it was focusing on three new short-term trials and would continue to evaluate data and other factors to inform the re-initiation of the paused studies.
Now, Sage has revealed the two trials will never restart. Sage took the action as it “does not believe that these studies will be required for a potential NDA submission.” The view on the necessity of the studies for the zuranolone application is informed by talks with the FDA, Sage said.
Sage originally proposed using data from REDWOOD to support the use of zuranolone as an episodic treatment for MDD. Management has played down the likelihood of needing additional data from the study in recent months, telling investors that the recent WATERFALL results and ongoing open-label SHORELINE study can provide the required evidence.
With WATERFALL hitting its primary endpoint in MDD, albeit with data that underwhelmed investors, Sage and partner Biogen are now planning to discuss next steps with the FDA. Sage has previously said it may be possible to seek approval on the strength of WATERFALL, but it may hold off until it has data from CORAL, another study in MDD.
CORAL is one of three studies that will shape the future of zuranolone. All of the clinical trials were previously due to read out late this year, but Sage revealed a delay to the phase 3 SKYLARK postpartum depression (PPD) study in conjunction with the release of its second-quarter results.
Sage now expects to have top-line data from the study around the middle of next year. The biotech attributed the delay to “a slower than anticipated pace of enrollment in the study due to a lower number of women seeking care for PPD and a lower rate of childbirth during the pandemic.” The number of babies born in the U.S. fell (PDF) 4% last year, sinking to the lowest level since 1979.