Sage Therapeutics' SAGE-547 meets main goal in Phase II postpartum depression trial

Shares in Sage Therapeutics gained as much as 48 percent Tuesday after the company announced top-line Phase II results demonstrating that its experimental intravenous therapy SAGE-547 significantly reduced severe postpartum depression (PPD) symptoms, compared with placebo. Samantha Meltzer-Brody, primary investigator for the PPD-202 trial, said "this is potentially one of the most important clinical findings in the pharmacologic treatment of postpartum depression to date." 

The randomised study was designed to enrol up to 32 women with severe PPD, defined as a score of at least 26 on the Hamilton Rating Scale for Depression (HAM-D), who developed severe depression either in the third trimester or within four weeks of childbirth. Sage noted that patients in both the SAGE-547 and placebo arms of the trial had mean HAM-D scores of more than 28 at baseline. The primary endpoint was change in the HAM-D score at 60 hours, while secondary objectives included the Montgomery–Åsberg Depression Rating Scale (MADRS).

According to Sage, SAGE-547 was associated with a mean reduction of more than 20 points in  depression scores at 60 hours through trial completion, with a greater than 12-point difference from placebo. The company noted that the significant difference in treatment efficacy began at 24 hours,"with an effect that was maintained at similar magnitude" through to the study's 30-day follow-up period.

Sage added that results from secondary efficacy endpoints, including other rating scales such as the MADRS, "reinforced the overall efficacy observed with SAGE-547 in the trial." Moreover, remission from depression, defined as a HAM-D score of 7 or less, was observed among seven of 10 treated patients at 60 hours, versus one out of 11 patients in the placebo arm. The company noted that the remission finding for the SAGE-547 group was maintained through to 30 days, indicating "a strong durability of effect" for over three weeks post-treatment. Meanwhile, two women in the placebo arm were in complete remission at 30 days. Sage said it would present detailed results from the trial at future medical meetings and in publications.

CEO Jeff Jonas suggested the PPD-202 results "speak for themselves," adding that "the unmet need in the PPD patient population cannot be overstated." He also noted that "as the second positive placebo-controlled trial involving SAGE-547, the first being in essential tremor, this demonstrates the potential broad utility of our differentiated GABA mechanism and the candidate molecules in our pipeline, not only for neurological disorders, but now for mood and affective disorders as well." 

Based on the PPD-202 findings, Sage expanded its mid-stage clinical programme to determine optimal dosing of SAGE-547 in PPD, with enrolment of both moderate and severe PPD patients set to begin this year. The company, which estimates that roughly 125 000 cases of severe PPD are diagnosed in the US each year, also intends to advance a PPD programme for SAGE-217, with plans to initiate multiple Phase II trials of the experimental oral therapy later this year, as well as seek regulatory input "to determine the appropriate pathways for developing both medications for this indication." Meanwhile, SAGE-547 is also being studied in the Phase III STATUS trial as a potential treatment for patients with super-refractory status epilepticus.

For more analysis on the PPD-202 trial results, see ViewPoints: A potential cure for the 'baby blues'? – 5 key takeaways from Sage Therapeutics' extraordinary Phase II data.

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