SAGE and PPD

SAGE Therapeutics’ remarkable run with tiny-n pilot studies as predictors of Phase II results continued when SAGE-547 separated remarkably well in a larger (albeit still very small, 21pt study) trial in severe Post-Partum Depression. A single injection provided remission of symptoms in seven of the ten patient SAGE-547 cohort (mean 20pt reduction or more in HAM-D) compared with one patient out of eleven (a mean 8pt HAM-D reduction) receiving placebo. MADRS score changes were similar. The impact was rapid, significant at 60 hours, and just as important, the impact was durable, remaining significant at thirty days. The initial pilot data had been viewed with skepticism by some, but as we noted in our March/April review of depression: “there was some appropriate skepticism about the predictive value of results from four depressed patients receiving an IV infusion of an experimental drug, a set-up for a placebo effect if ever there was one. But the premise for SAGE-547 in PPD has a solid biological basis: SAGE-547 is, after all, a form of allopregnanolone, and women with PPD have been reported to have lower levels of endogenous allopregnanolone than their nondepressed post-partum peers. It has thus been suggested that allopregnanolone may be protective against PPD.”  And so it appears to be, though it remains to be seen what scale of pivotal testing will be required by the FDA. This is not a large patient population (200,000-600,000 US cases annually), but when one considers the locus of PPD’s effect on a critical developmental time period for a newborn, the human impact of the disorder, and the potential of a successful treatment, are considerably magnified.

from NeuroPerspective March-April 2016
Post-Partum-Depression
Pregnancy and new motherhood are often very different from the idealized, bucolic images conveyed by advertisers, churches, and aspiring grandparents. Indeed, somewhere between 5% and 25% of women experience some degree of post-partum depression. Some of them may have had a history of depression, and because of lingering worries about the safety of perinatal exposure to antidepressants, discontinued their antidepressants during pregnancy. Similarly, women who are nursing may be reluctant to use antidepressants, leaving them ill-equipped to content with their affective disorder. Combine that with the hormonal and experiential upheavals that go along with childbirth and new motherhood, these women can be vulnerable to a dramatic return and exacerbation of depressive symptoms. For a very tiny percentage, this can turn into a psychotic depression, with rare, but on highly-publicized occasion, horrific results.
In June 2015, SAGE Therapeutics announced results from their pilot data in Post-Partum Depression (PPD) and temporarily boosted their market cap by about $420 million. A planned fifteen patient study was cut short after the first four patients showed a complete reversal of their depression, their Hamilton scores nearing zero 60 hours later. SAGE immediately recognized that this radical improvement in PPD symptoms was well-deserving of a placebo-controlled study. At the same time, there was some appropriate skepticism about the predictive value of results from four depressed patients receiving an IV infusion of an experimental drug, a set-up for a placebo effect if ever there was one.
But the premise for SAGE-547 in PPD has a solid biological basis: SAGE-547 is, after all, a form of allopregnanolone, and women with PPD have been reported to have lower levels of endogenous allopregnanolone than their nondepressed post-partum peers. It has thus been suggested that allopregnanolone may be protective against PPD.
SAGE will develop a different, orally bioavailable molecule for PPD, once the signal has been confirmed. That confirmation is hoped to come from a 32pt Phase II placebo-controlled trial that should be completed by midyear.

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One Response to SAGE and PPD

  1. mike says:

    The NIA in 2014 started an Allopregnanolone trial in 24 MCI patients over 12 weeks. Noticed Dr Brinton is presenting on it at the upcoming AAIC on July 27th. Allo has positive animal data showing neurogenesis and reduced amyloid. Longshot but odds of hitting better after PPD data. http://www.investorvillage.com/smbd.asp?mb=17990&mn=13&pt=msg&mid=16154898

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