Sage Therapeutics Looks to File NDA for Postpartum Depression Treatment Later This Year

Cambridge, Mass.-based SAGE Therapeutics closed out 2017 with stellar results for a mid-stage and late-stage trial aimed at treating two kinds of depression.

In December, the company released positive topline results for its Phase II treatment for patients with moderate to severe major depressive disorder (MDD). Those results came on the heels of two Phase III clinical trials testing lead product brexanolone, an allosteric modulator of both synaptic and extrasynaptic GABAA receptors, in patients with severe postpartum depression (PPD) and moderate postpartum depression. Brexanolone hit the mark in both trials.

Now two weeks into the New Year, Sage is planning to file a New Drug Application with the U.S. Food and Drug Administration seeking approval for brexanolone in postpartum depression. Last year, the FDA granted brexanolone Breakthrough Therapy Designation for that indication. It received a similar status from the European Medicines Agency. Brexanolone is in Phase III for postpartum depression.

If brexanolone is approved, it will be a game changer for women diagnosed with PPD. Sage Chief Medical Officer Steve Kanes told BioSpace in an exclusive interview that brexanolone would be the first FDA drug approved by the U.S. Food and Drug Administration for severe PPD.

"It’s been a very efficient clinical development," Kanes said of brexanolone from the J.P. Morgan Healthcare Conference in San Francisco. "Within two-and-a-half days, women showed rapid and profound improvement in depression scores. Patients get better and they get better in a hurry."

Jim Doherty, head of research at Sage, said targeting the GABA receptor system allows the company to treat brain function something like a dimmer switch. The drug allows brain excitability to be "turned up or down," Doherty said.

"In depression, there is some hyperexcitable circuitry in the brain and the GABA platform can help that," Doherty said.

Kanes said the company anticipates filing the NDA in the first half of this year with plans to be on the market in the early part of 2019. The filing of the NDA will be a key milestone for the company as the timeline for the indication will be about three years from start to finish, Kanes said.

During J.P. Morgan, Sage provided an update on its long-term strategy to drive growth at the company. A core component of that is developing therapies for the CNS that are unmet, or little served, such as forms of depression.

In addition to the planned NDA for brexanolone, Sage will also move forward with SAGE-217, its Phase II treatment for patients with moderate to severe major MDD. In December, the company released trial results that showed SAGE-217, a positive allosteric modulator optimized for selectivity to synaptic and extrasynaptic GABA receptors, provided profound, rapid and durable reduction in depressive symptoms for two-thirds of trial participants within days.

In addition to MDD, Sage is also exploring SAGE-217 for use in additional indications such as Parkinson’s disease and insomnia.

"These are all areas that the drug shows particular utility," Kanes said.

While the company has shown positive results in the areas of depression, particularly with brexanolone, the experimental treatment did stumble dramatically last year in a late-stage trial as potential treatment for a severe form of epilepsy. Phase III trial data showed that brexanolone failed to differentiate itself from placebo. While the results were disappointing, Kanes said the company will take a deep dive into the data to understand what went wrong, particularly after the drug had shown promise in earlier trials.

Sage isn’t resting on the two drugs though. It has multiple projects in development for a number of indications. Kanes said the company plans to file an Investigational New Drug application for SAGE-324 for a movement disorder and epilepsy.

As 2018 moves forward Kanes and Doherty said the company will articulate its overall strategy later this year. In February, the company will provide specific 2018 financial guidance in its fourth quarter and full year 2017 financial results.