Zuranolone or SAGE-217 is similar to brexanolone (marketed as Zulresso), the medication which was FDA-approved for the treatment of postpartum depression. Zuranolone is a neurosteroid, an analogue of allopregnanolone, which is a positive allosteric modulator of the GABA-A receptor. What distinguishes zuranolone from brexanolone is that it has much better oral bioavailability and thus does not have to be administered intravenously. It can be taken as an oral medication, just like conventional antidepressants.
While data regarding the use of zuranolone for non-perinatal major depression (the MOUNTAIN study) looked a little iffy, the Phase 3 data looking at zuranolone for the treatment of postpartum depression (the ROBIN study) suggested that zuranolone has antidepressant effects in women with severe PPD. Also important was the finding that there were no concerning side effects.
What’s Next for Zuranolone?
We’ve been waiting to see what would happen next with zuranolone. Sage Therapeutics announced that it will continue to develop zuranolone as an oral therapy for women with PPD. In order to support an efficacy claim for PPD, they will need to conduct one additional positive pivotal trial to complement the findings of previously completed studies. Although these studies only followed women for 30 days after treatment, Sage reports that no additional long-term follow-up is expected to be required by the FDA.
They anticipate conducting one additional placebo-controlled trial evaluating a two-week course of zuranolone (50 mg) in women with PPD and anticipate that they will have data from that trial in 2021.
We look forward to seeing more data on zuranolone. We were excited about brexanolone; however, its launch has been complicated. Not only does brexanolone have to be administered as a 60-hour intravenous infusion, the FDA has raised concerns about two serious adverse events: suicidal ideation after the infusion in one subject and syncope/altered consciousness in another patient. Because of these concerns, Zulresso was approved with a Risk Evaluation and Mitigation Strategy (REMS) and “will only be available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.” No such worries for zuranolone.
Ruta Nonacs, MD PhD