Sage Therapeutics has shared data from an open-label trial of zuranolone as it starts to remake the case for the drug following its phase 3 failure. The study found around half of major depressive disorder (MDD) patients who respond to zuranolone require retreatment and that outcomes for subsequent courses are comparable to the initial treatment.
Late last year, the failure of zuranolone, also known as SAGE-217, to outperform placebo in terms of improving scores on a depression scale at Day 15 forced Sage to rethink its development strategy. Sage emerged from the process with plans to run three new clinical trials of zuranolone and tweak its existing roster of studies, including by adding a higher, 50-mg dose to its SHORELINE open-label trial.
Sage shared data from SHORELINE on Thursday. The most mature data come from the 30-mg dose arm that was underway at the time of the R&D rethink. Participants received 30 mg of zuranolone, an oral formulation of Sage’s approved infused drug Zulresso, once nightly for 14 days.
Eighty percent of the 725 MDD patients in the 30-mg cohort responded to the drug and continued into the naturalistic follow-up period. Sage said 458 patients had partial responses, and 255 went into remission.
After the initial treatment stage of the study, investigators continued to track, and in some cases treat, 494 responders. Sage said 55.5% of those patients required retreatment with at least one more course of zuranolone. Around 15% of the initial responders received four or more additional courses of zuranolone. Most patients only received one or two courses, though.
“Approximately 70% of patients who participated in the study only needed one or two treatment courses, a total of two to four weeks of treatment with zuranolone 30 mg, which we believe will be the minimally effective dose, if our development efforts are successful,” Sage CEO Jeff Jonas, M.D., said in a statement.
The safety and efficacy outcomes associated with subsequent courses of zuranolone were similar to those achieved by the initial treatment. Participants who continued on a preexisting antidepressant therapy—who made up 42% of the initial 725-subject population—required a similar number of retreatments as their peers who only received zuranolone.
Sage also shared an early look at data on the use of 50 mg of zuranolone, which investigators began giving to retreated patients in May. A new 50-mg cohort of patients just starting on zuranolone got underway at the same time.
Higher rates and levels of intensity of adverse events were seen in the 48 patients who switched from 30-mg to 50-mg dosing for retreatment, although most events were still mild or moderate. In the 76 patients with safety data available from the 50-mg cohort, somnolence, dizziness, sedation, headache and tremor—events that happened more than 5% of the time—were more frequent, but the severity was similar to in the 30-mg group.
Almost half of the 52 patients in the newly dosed 50-mg cohort entered remission. That compares favorably to the remission rate in the 30-mg group. The mean change from baseline in depression score was numerically bigger in the 50-mg group, too, although the differences could disappear as more patients receive the higher dose.