Sage Therapeutics Erupts as Depression Drug Wows in Mid-Stage Study

Shares of Sage Therapeutics have shot up more than 75 percent this morning after the company announced positive topline results for its Phase II treatment for patients with moderate to severe major depressive disorder (MDD).

In an announcement this morning, Sage said its experimental treatment SAGE-217, a positive allosteric modulator optimized for selectivity to synaptic and extrasynaptic GABA receptors, met both primary and secondary endpoints in its trial. The once-daily oral treatment provided profound, rapid and durable reduction in depressive symptoms for two-thirds of trial participants within days.  Additionally, SAGE-217 was generally well-tolerated with no serious or severe adverse events, the company said.

Sage Chief Executive Officer Jeff Jonas hailed the results as a treatment for MDD, a mood disorder in which patients exhibit depressive symptoms, such as a depressed mood or a loss of interest or pleasure in daily activities consistently for at least a two-week period. Patients diagnosed with MDD typically have a difficult time functioning in social or work-related functions. MDD effects an estimated 16 million people in the United States.

Jonas noted that there has been "little innovation" in the development of new treatments for depression over the past 20 years. Antidepressants are widely used for treatment of MDD.

Sage Chief Medical Officer Steve Kanes said there are "significant gaps" in depression management and the goal at Sage is to "change patients’ expectations by transforming the treatment landscape for MDD."

By the end of 15 days of treatment with SAGE-217, 64 percent of patients achieved remission of MDD. That was compared to 23 percent on placebo, the company said. In the Phase II MDD trial, treatment for 14 days with SAGE-217 was associated with a statistically significant mean reduction in the Hamilton Rating Scale for Depression (HAM-D) of 17.6 points for SAGE-217, compared to 10.7 for placebo. Statistically significant improvements were observed in the HAM-D compared to placebo by the morning following the first dose through Week 4 and the effects of SAGE-217 remained numerically greater than placebo through the end of follow-up at Week 6, the company said.

The Phase II topline results was announced less than one month after the company announced the success of two Phase III clinical trials testing brexanolone in severe postpartum depression and moderate postpartum depression. Brexanolone hit the mark in both trials.

"Coupled with our recent positive Phase III data read-out evaluating brexanolone for the treatment of postpartum depression, the findings in this study suggest our pipeline of proprietary GABAA modulators may impact novel and fundamental brain mechanisms, offering potential development opportunities in a variety of indications. The positive activity and safety findings of SAGE-217 in MDD support advancing the program into later stage clinical development and we will work with the FDA to determine next steps in the further development of SAGE-217," Jonas said in a statement.

The Phase III success though came on the heels of a significant Phase III failure of brexanolone to help patients with a severe form of epilepsy. Brexanolone (Sage-547) failed miserably to differentiate itself from placebo in treating patients with super-refractory status epilepticus (SRSE), which is a severe form of the disease that causes seizures that last longer than five minutes.