About a year ago, we first reported on SAGE-547 (SAGE Therapeutics), a new medication for the treatment of severe postpartum depression. SAGE-547 is a new drug, an allosteric modulator of GABAA receptors, which was initially under investigation for the treatment of refractory seizure disorders. It turns out that SAGE-547 may also be useful for the treatment of severe postpartum depression (PPD).
Today Sage Therapeutics announced positive results from its Phase 2 clinical trial of SAGE-547 for the treatment of severe postpartum depression. The women included in this placebo-controlled, double-blind, randomized trial had severe depressive symptoms with a score of at least 26 on the Hamilton Depression Rating Scale (HAM-D). The Major Depressive Episode began no earlier than the third trimester and no later than the first four weeks following delivery. At the time of enrollment, all women were less than six months postpartum.
The participants were randomized to receive either SAGE-547 (n=10) or placebo (n=11) as a blinded intravenous infusion taking place over 60 hours.
At 24 hours, participants receiving SAGE-547 experienced a 19.0 point mean reduction in their HAM-D scores (p=0.006), compared to 8.4 points in the placebo group. Seven of the ten participants receiving SAGE-547 achieved remission from depression (as defined as a HAM-D score of < 7) assessed at 60 hours, as compared to 1 of 11 placebo patients (p=0.008).
When the first open trial of SAGE-547 came out last year, one of the questions we had was related to the longevity of the beneficial response. The good news from this study is that the reduction in HAM-D scores and remission were maintained through to the 30-day follow-up timepoint.
SAGE-547 was well tolerated; there were no serious adverse events, and no women discontinued treatment. Adverse events were less commonly reported in the participants receiving SAGE-547 (4 of 10) as compared with placebo (8 of 11). The most common side effects were dizziness, sedation, and somnolence, seen at similar rates in both groups of participants.
This is a preliminary study, and we look forward to reviewing the data when it is published. Nonetheless, the findings presented in the press release are pretty impressive. The women included in this study had severe postpartum depression, and SAGE-547 may be a new and much-needed option for this group of women.
One of the most exciting things about SAGE-547 is the rapidity of the response — remission of depression within 24 hours! Because antidepressants typically take 2-4 weeks to kick in, an antidepressant agent with rapid onset of action would be particularly appealing to women with severe PPD, particularly women with suicidality. It appears that the positive response lasts for at least 30 days.
One of the downsides of SAGE-547 is that it must be given intravenously. According to its press release, Sage Therapeutics is moving forward with a PPD program involving a similar compound which is intended for once-daily oral dosing. We look forward to hearing more about these novel treatments for PPD.
Ruta Nonacs, MD PhD