Drug Development

Sage claims another big win on a small study, this time for postpartum depression

Shares of Sage Therapeutics $SAGE rocketed up 38% this morning after the Cambridge, MA-based biotech posted remarkable data from a small study of its lead drug for postpartum depression.

So far, Sage has concentrated much of its attention touting the impact of SAGE-547 on rare cases of protracted seizures called super-refractory status epilepticus. But CEO Jeff Jonas has also been pursuing a theory that the drug can have an impact on mood disorders like depression, a tough field that has seen a series of painful pratfalls by developers over the years.

In this latest study, Sage says that the drug–aimed at GABAA receptors in the brain–hit the primary endpoint in the Phase II, which involved only 21 patients; and only a few patients actually got the drug. Investigators tracked a 60% remission rate at 60 hours with a 30-day follow-up.

Sage reported:

Remission from depression, as determined by a HAM-D ≤7, measured at 60 hours, was seen in 7 of 10 of the SAGE-547 group compared with 1 of 11 in the placebo group (p=0.008). Similarly, at 30 days, 7 of 10 of the SAGE-547 group and 2 of 11 in the placebo group were in remission (p=0.03).

That’s a major difference in outcomes, but it still only involves a tiny number of patients, which could heavily skew the outcome. To put this in some perspective, Alkermes’ two failed Phase III studies for their depression drug involved more than 800 patients with a much higher placebo response. And a third Phase III has yet to read out.

The next step at Sage will be to expand the small study in search of an optimal dose. But the small number of patients involved so far certainly didn’t stop the company from claiming a huge win. Sage confidently outlined a big role for itself in some risky fields, including major depression, bipolar disorder, and panic disorder.

Samantha Meltzer-Brody, M.D., M.P.H., Associate Professor and Director of the UNC Perinatal Psychiatry Program

Samantha Meltzer-Brody, M.D., M.P.H., Associate Professor and Director of the UNC Perinatal Psychiatry Program



“The rapid onset of action of this drug observed in the trial is unlike anything else available in the field to date,” said Samantha Meltzer-Brody, M.D., M.P.H., Associate Professor and Director of the UNC Perinatal Psychiatry Program of the UNC Center for Women’s Mood Disorders and primary investigator for the PPD-202 Trial. “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.”

Sage has a history of finding reasons for its investors to be super-excited about its data. But it’s also been under attack by short sellers at Sahm Adrangi’s Kerrisdale Capital. Adrangi’s group has ridiculed the company’s data on brain seizures, saying the company went from a small study into a Phase III that it was doomed to flop in.

With Sage’s stock way up today, the longs and the shorts will be at each other’s throats. One group will win big; another will lose a huge amount.

But that jury is still out. The FDA typically requires several big late-stage studies for any drug when it comes to depression, simply because of the impact of a highly variable placebo effect. If Sage can survive that process, the sky’s the limit. But a history of failures might be cause for caution.

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