Biogen and partner Sage Therapeutics on Tuesday said they plan to seek FDA approval of zuranolone in the second half of 2022, with a rolling submission expected to start early in the year. The initial submission package will seek approval of the drug, which is given once-daily for two weeks, to treat major depressive disorder (MDD), while another filing in postpartum depression (PPD) is slated for the first half of 2023 (see ViewPoints: Sage sets course for depression hopeful ).
Biogen shelled out $875 million  upfront last year in a deal to co-develop zuranolone with Sage for both MDD and PPD, as well as another drug for essential tremor. The partnership could ultimately be worth another $1.6 billion for Sage, in which Biogen also took a $650-million equity stake.
Zuranolone, formerly SAGE-217, appeared on shaky ground in 2019 when it failed to outperform placebo in the Phase III MOUNTAIN trial of patients with MDD. At the time, Sage suggested some patients had not been taking their medication properly, and it also noted that significant improvements in depression were seen among people who had received the higher dose.
Earlier this year, the companies reported that another late-stage trial, dubbed WATERFALL, had met  its primary endpoint of significantly improving depressive symptoms compared to placebo, although the data raised questions about the drug's efficacy over the longer term (for more, see KOL Views Q&A: Leading psychiatrist says zuranolone works but intermittent dosing is a double-edged sword ).
On Tuesday, the companies said the decision to move ahead with the FDA application follows recent discussions with the regulator. Barry Greene, chief executive at Sage, touted a "solid filing package [for zuranolone] with four adequate and well controlled trials now in hand," and said the FDA's feedback at a pre-NDA meeting held this fall "continued to be consistent with previous discussions."
Included in the submission packages will be data from two development programmes evaluating the drug in MDD and PPD. The LANDSCAPE programme comprises five studies, including MDD-201B, MOUNTAIN, SHORELINE, WATERFALL and CORAL. The companies noted that this last trial, which is testing zuranolone co-initiated with a standard antidepressant therapy, is now fully enrolled, with top-line data expected in early 2022.
Biogen's head of R&D Alfred Sandrock said the companies believe they have found an "efficient filing pathway" for zuranolone, with efficacy and safety data that "support our vision of zuranolone being an as-needed, two-week, once-daily treatment option for MDD and PPD that produces rapid relief from symptoms within days."
Meanwhile, the NEST programme includes the ROBIN and SKYLARK trials. Sage and Biogen said they plan to submit a separate filing for PPD once the ongoing SKYLARK trial completes "so as not to affect the MDD review timeline." They suggested that the review cycles may allow commercialisation of both the MDD and PPD indications simultaneously, if approved. The FDA cleared  Sage's Zulresso (brexanolone) for PPD in 2019.
Have a look at this psychiatrist survey  FirstWord conducted after the WATERFALL readout for a peak at their take on those results.