Sage Bounces Back, Eyes FDA Filing for Postpartum Drug

Xconomy Boston — 

There may be a new treatment on the horizon for postpartum depression, an often severe form of depression that affects women after childbirth. Sage Therapeutics reported this morning that an experimental neurological drug known as brexanolone succeeded in two Phase 3 trials, setting the stage for an FDA approval filing next year.

Cambridge, MA-based Sage (NASDAQ: SAGE) said brexanolone hit its main goal in both trials, which tested the drug in women with either moderate or severe PPD. The drug led to a statistically significant reduction, compared to a placebo, in a measure of patients’ depression symptoms known as the HAM-D scale 60 hours after they were treated. Sage said patients on its drug in both trials saw their HAM-D scores fall an average of 14 to 20 points after 60 hours. In patients with severe PPD, the results held up after a month, also with statistical significance.

The most common side effects seen in the trials were headaches, dizziness, and drowsiness. In each study, one patient had an unspecified serious side effect. Sage said neither of those side effects, however, led to a hospital stay and one of them wasn’t related to treatment with brexanolone. Sage will file for FDA approval of the drug next year.

Shares of Sage climbed more than 29 percent, to $81 apiece, in pre-market trading on Monday. The company will hold a conference call this morning to discuss the data.

PPD affects an estimated 10 to 20 percent of women giving birth in the U.S., according to Sage. There are no treatments specifically approved for the condition.

In the two studies, Sage enrolled 122 patients with severe PPD, and 104 patients with moderate PPD.

Patients with severe PPD were split into three groups and given either a low dose of brexanolone, a high dose, or a placebo. Those on a low dose saw their HAM-D scores fall an average of 19.9 points 60 hours after treatment, compared to a 17.7 point reduction for those on a high dose and a 14.0 point change for placebo patients. The drug’s effects appeared to kick in at 48 hours and held up, for both doses, through 30 days.

Patients with moderate PPD got either a high dose of brexanolone or a placebo. High dose patients saw their HAM-D scores fall 14.2 points, compared to a 12 point fall for those on placebo, after 60 hours. Sage, however, said the effects in patients with moderate PPD were statistically significant after 7 days, but not 30.

In a note to investors, Leerink Partners analyst Paul Matteis said the results don’t quite match the “too good to be true” results the drug posted in earlier studies—in a Phase 2 trial published in the peer reviewed journal the Lancet, the drug’s HAM-D scores were close to 12 points better than a placebo. But the data are nonetheless a “technology validating event” for the company, Matteis wrote, and will likely lead to FDA approval. A second Sage drug, SAGE-217, is being tested in major depressive disorder, with results expected later this year.

Indeed, the news marks a big victory for Sage, which saw brexanolone stumble in its first big test in September when the drug failed a Phase 3 trial in super refractory status epilepticus, a rare form of epilepsy. The drug’s failure in the trial increased skepticism that it might succeed in PPD—a far more lucrative opportunity for the company—but Sage executives were adamant that brexanolone’s failure in SRSE wasn’t a harbinger of similar problems in the PPD trials. On a conference call in September, CEO Jeff Jonas cited differences in the diseases themselves, the variability in the underlying cause that led to patients’ SRSE, and the “consistency of data” the drug had generated to that point in PPD. “We’re very confident with the science,” he said.

Nonetheless, there was reason for skepticism. While Sage reported encouraging results from a placebo-controlled Phase 2 trial last year, those data were from a tiny, 21-patent study. And depression studies are notoriously troublesome due to high placebo responses that can doom trials and make results difficult to interpret. The results Sage reported today, however, mean the company, which went public in 2014 at $18 a share, has a chance to begin selling its first product.

“We believe the data represent an unprecedented opportunity in the development of treatments for PPD, and may serve as the catalyst for a paradigm shift in how the disease is approached and, if approved, may change how PPD is treated,” Jonas said in a statement.