Sage Therapeutics, Inc. announced next steps in the Landscape Program, the clinical program evaluating zuranolone (SAGE-217) for the treatment of postpartum depression (PPD) and major depressive disorder (MDD) , following a Breakthrough Therapy guidance meeting with the FDA. Sage has identified three potential pathways intended, if successful, to support a possible filing for approval of zuranolone in the U.S. in two novel indications – PPD and acute treatment of MDD when co-initiated with a new antidepressant – along with the previously disclosed development plan for the treatment of MDD as an episodic therapy.
Zuranolone Landscape Program : The Landscape Program is evaluating the potential of zuranolone as a rapid-acting, short-course oral treatment for PPD and MDD. It includes three completed pivotal efficacy studies evaluating zuranolone 30 mg in PPD (ROBIN Study) and MDD (MDD-201, MOUNTAIN Study), the results of which have been previously reported.
Planned studies to support multiple filing pathways : Following discussions with the FDA, Sage plans to initiate three new short-term clinical studies in 2020 , with the potential, if successful, for three distinct indications: PPD, acute rapid response therapy in MDD when co-initiated with a new standard antidepressant, and episodic treatment of MDD. These planned studies include: 1. For use as an oral therapy in women with PPD : one additional positive pivotal trial, along with data from previously completed studies, is expected to be required to support an efficacy claim in PPD. No additional long-term follow-up is expected to be required to support an efficacy claim in this indication: Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg in women with PPD, with additional short-term follow-up. Topline data from this study is anticipated in 2021. 2. For use as an acute rapid response therapy (RRT) in patients with MDD when co-initiated with new standard antidepressant therapy : one additional positive treatment study, along with data from previously completed acute treatment studies, is expected to be required to support an efficacy claim in this indication: Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg, when co-initiated with an open-label SSRI, in patients with MDD, with additional short-term follow-up. Topline data from this study is anticipated in 2021. 3. For use as an episodic therapy in patients with MDD: one additional positive pivotal trial, along with previously completed acute treatment studies and long-term safety data, including data from REDWOOD (MDD-302) , are expected to be required to support an NDA filing for episodic treatment of depression: Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg in patients with MDD, with additional short-term follow-up. Topline data from this study is anticipated in 2021.
Updates to three ongoing or paused studies : SHORELINE Study (MDD-303): The Company is on track to report topline data in 2020 from patients with MDD who received zuranolone 30 mg in the SHORELINE Study. The protocol has been amended to allow currently enrolled patients to receive retreatment with zuranolone 50 mg. Additionally, the Company expects to enroll a new cohort of patients with MDD who will receive zuranolone 50 mg. REDWOOD Study (MDD-302) : The Company paused enrollment in the REDWOOD study in the fourth quarter of 2019 and plans to reevaluate timing for reinitiating the study while resources and activities focus on enrollment in the three new planned Phase III clinical studies. RAINFOREST Study (MDD-304): The Company paused enrollment in the RAINFOREST study in the fourth quarter of 2019. The Company plans to evaluate data from ongoing and planned short-term studies prior to reinitiating enrollment.
The Company is also currently evaluating the ongoing zuranolone clinical pharmacology and safety program and plans to finalize requirements to support a potential future new drug application (NDA) with the FDA..
Comment: A failed study, called MOUNTAIN, was intended to support an application for approval to the FDA. Without it, Sage has been forced to redraw its plans, leading to the current update.