An experimental Sage Therapeutics drug intended to alleviate depression symptoms quickly failed to beat a placebo in a pivotal study, the company reported Thursday.
Cambridge, MA-based Sage (NASDAQ: SAGE) has been testing its drug, SAGE-217, as a treatment for the symptoms of major depressive disorder. Unlike many depression drugs, which need weeks to take effect and must be taken chronically, the Sage drug was developed to provide relief much sooner. The main goal of the Phase 3 study was to show a reduction in symptoms after 15 days, as measured by a scale used to assess depression.
Sage says patients given the once-a-day pill showed an average reduction of 12.6 on the scale, which was not enough to distance itself from the 11.2 average reduction reported for the placebo group. Further analysis revealed that approximately 9 percent of patients in the group given SAGE-217 showed no measurable concentration of the drug—consistent with patients who were not compliant with instructions to take their medication. When those patients are excluded from the analysis, Sage says the remaining data showed statistical significance for its drug all the way through day 15 of the study. But investors still frowned on the results, and shares of Sage sank more than 60 percent in pre-market trading.
The SAGE-217 results released Thursday fell short of the Phase 2 data. After 15 days, patients treated with the drug in that study showed an average 17.6 reduction on the depression scale compared to an average 10.7 percent reduction in the placebo group. Last year, the FDA said just one 450-patient Phase 3 study for SAGE-217, not two, would be sufficient for regulatory review. That put the drug on a potentially faster pathway to approval. But developing drugs for depression has been notoriously difficult, as experimental psychiatric medicines are stymied in larger studies by the placebo effect.
The latest SAGE-217 results now raise questions about the drug’s prospects for other conditions. The drug is currently being tested in pivotal postpartum depression (PPD) study; it’s hoped the drug can offer an alternative to Sage’s own drug for the condition, brexanolone (Zulresso). That drug was approved earlier this year as the first medication specifically developed for PPD. But it requires a 60-hour infusion in a medical facility. As a pill, SAGE-217 would be more convenient for patients. Besides PPD and major depressive disorder, the Sage pill is being tested in pivotal studies in comorbid major depressive disorder and treatment-resistant depression.