July 12, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Massachusetts - Sage Therapeutics announced the results of a Phase II clinical trial of SAGE-547 to treat severe postpartum depression (PPD) today, with highly positive results.
The study’s primary endpoint was a significant reduction in the HAM-D score compared to placebo at 60 hours. Sage found a 20 point mean decrease in the depression score in the group receiving Sage-547, with a better than 12 point difference. Furthermore, the statistically significant difference was observed at 24 hours, which continued throughout the 30-day follow-up.
“This is potentially one of the most important clinical findings in the pharmacologic treatment of postpartum depression to date,” said Samantha Meltzer-Brody, primary investigator for the PPD-202 Trial, and associate professor and director of the UNC Perinatal Psychiatry Program of the UNC Center for Women’s Mood Disorders, in a statement. “The rapid onset of action of this drug observed in the trial is unlike anything else available in the field to date. The data show the potential of the drug to provide relief from the debilitating symptoms of PPD, and to markedly decrease suffering in women who are severely affected.”
The study’s secondary endpoints, which included the Montgomery-Asberg Depression Rating Scale (MADRS), were similar. Sage has begun to expand the Phase II program to help identify optimal dosing, and will evaluate patients with both moderate and severe PPD. It also plans to continue work on its oral molecule, SAGE-217, in PPD.
Sage Therapeutics spiked at the news. On Dec. 21, 2015, shares traded for $59, then dropped to $28.63 on Feb. 8, 2016. Shares rose to $39.42 on April 21, then dropped to $26.96 on June 27. Shares traded for $34.36 yesterday and are currently trading for $48.66.
“These data speak for themselves,” said Jeff Jonas, Sage’s chief executive officer, in a statement. “The unmet need in the PPD patient population cannot be overstated. Given the societal impact of this condition, and the possible identification of a biological basis for treating these women, we are hopeful these data will point to a new understanding of this disorder and the development of effective therapies. Furthermore, as the second possible 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.”
Of the participants in the study receiving the drug, 70 percent had complete remission, no more depression, after 60 hours, versus slightly less than 10 percent of women who received the placebo injection.
There are no approved treatments specifically for PPD. PPD affects 10 percent to 15 percent of mothers. Symptoms include severe anxiety, panic attacks, thoughts of harming herself or the baby, feelings of worthlessness, shame, guilt and inadequacy.
Sage-547 is a hormone that stimulates neurotransmitter receptors dubbed GABA in the brain. According to Adam Feuerstein, writing for TheStreet, “Sage believes the specific and differentiated ways in which Sage-547 targets the GABA receptor explains the drug’s potential benefit against a list of central nervous system diseases, including epilepsy, movement disorders, postpartum depression and anxiety.”
What makes postpartum depression particularly of interest is that the disease varies from major depressive disorder because it is caused by increasing and decreasing amounts of various hormones during pregnancy and after birth. This causes the GABA system to get out of balance.
The drug is also being investigated in a Phase III trial in super-refractory status epilepticus, a particularly severe form of epilepsy. Data is expected in the second half of 2016.
