Biogen/Sage’s Zuranolone Data May Not Be Enough For Tough Commercial Landscape

 Although Sage Therapeutics, Inc.’s Phase III WATERFALL trial of zuranolone in adults with major depressive disorder (MDD) was positive, the benefit seen and its adverse event profile have raised doubts about its clinical meaningfulness, even if the data are sufficient to warrant US Food and Drug Administration filing.

The antidepressant, an oral neuroactive steroid GABA-A receptor positive allosteric modulator, has been a major focus for the firm, which made history with the approval of its first approved product; the intravenous postpartum depression drug Zulresso (brexanolone) was approved in 2019, but the experience on the market has been disappointing. Instead, focus shifted to Sage’s pipeline products – primarily zuranolone (SAGE-217), which had breakthrough designation at the FDA and offered the promise of an easier route of administration, but disappointed in its first Phase III trial