Sage Therapeutics disclosed another clinical trial victory this morning, sending shares of the Cambridge, MA, company to new highs. An experimental Sage drug for major depressive disorder (MDD), a psychiatric disease that affects millions of Americans, has succeeded in a Phase 2 study and will now head into late-stage testing.
Sage (NASDAQ: SAGE) said that experimental SAGE-217 met its main goal in an 89-patient, placebo-controlled Phase 2 study. 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 15 days after beginning treatment.
Sage said patients on its drug in both trials saw their HAM-D scores fall an average of 17.6 points after 15 days, compared to an average 10.7-point reduction in scores for placebo patients. Patients on SAGE-217 and placebo started the study with average HAM-D scores of 25.2 and 25.7, respectively.
After 15 days, 64 percent of patients on the Sage drug had a HAM-D score of 7 or less—a secondary goal of the study—compared to 23 percent of placebo patients.
Patients in the study were on SAGE-217 or a placebo for 15 days and were tracked for an additional four weeks afterwards. Even though patients were no longer on the treatment, the company said it saw statistically significant improvements on HAM-D scores hold through four weeks, compared to the placebo. Specifically: HAM-D scores fell 15.6 points for SAGE-217 patients and 11.9 points for placebo patients after four weeks. Those numbers narrowed to 15 points and 13 points, respectively, after six weeks, and were no longer statistically significant.
Similarily, 52 percent of people on SAGE-217 had HAM-D scores of 7 or less after four weeks, compared to 28 percent of placebo patients. Those numbers were 45 percent for SAGE-217 patients and 33 percent for placebo patients and weren’t statistically significant after six weeks.
The most common side effects reported were headache, dizziness, nausea, and drowsiness. Sage said two people on SAGE-217 dropped out of the study, versus no placebo patients.
Sage CEO Jeff Jonas said in a statement that the company will now meet with the FDA to determine the next steps in development for SAGE-217. Sage is also developing the drug—a once-daily pill that targets a neurotransmitter called GABA—for Parkinson’s disease, essential tremor, and postpartum depression.
The data, according to a note from Leerink Partners analyst Paul Matteis, are a “best-case scenario” for Sage. “It’s hard to understate how meaningful these data are in the backdrop of the very significant unmet medical need in depression,” Matteis wrote.
Sage will hold a conference call this morning to discuss the news.
Still, it is important to note that Sage will have to replicate these results in further testing, and a slew of drugs for mood disorders have succeeded in early testing only to fall flat, or paint a more mixed picture, later on. Drugs for depression or schizophrenia from Alkermes, now-defunct Forum Therapeutics, Intra-Cellular Therapies, and others have all seen higher than expected placebo effects crop up in large-scale psychiatric drug trials, either causing studies to fail or dooming clinical development altogether. Nonetheless, investors were emboldened by Sage’s results, sending shares skyrocketing 63 percent on Thursday morning to all-time highs of $149 apiece in pre-market trading.
Sage has already shown it can succeed with a depression drug in a Phase 3 trial. Its most advanced drug prospect, brexanolone, succeeded in two placebo-controlled Phase 3 studies in postpartum depression (PPD) earlier this year, setting the stage for an FDA filing. A pivotal study in MDD, however, will represent an even bigger challenge—and potential payoff if SAGE-217 can come through. PPD affects an estimated 10 to 20 percent of women giving birth in the U.S., according to Sage, but the prevalence of MDD is even higher. An estimated 16 million Americans suffer from MDD, and while marketed antidepressants are effective for some, they typically don’t kick in for a few weeks. Many patients don’t respond to treatment at all.
“If successfully developed, SAGE-217 has the potential to offer the first truly new mechanism of action in the pharmacologic treatment of depression in more than 20 years,” said chief medical officer Steve Kanes, in a statement.
Here’s more on Sage, and the trouble companies have had developing depression drugs.