Sage Therapeutics has released complete data from a 12-month study of patients taking 30 mg of the investigational oral neuroactive steroid zuranolone for major depressive disorder (MDD) and interim data on a cohort receiving a 50 mg dose.
“Today we are announcing additional positive data from the SHORELINE Study that demonstrate continued strong results from the 30 mg dose and strengthens our confidence in the potential of the 50 mg dose,” said Sage chief executive officer Barry Greene. “Designed as a naturalistic study, these data approximate real-world evidence of use of zuranolone at 30 mg and 50 mg doses.”
Zuranolone, a GABAA receptor positive allosteric modulator, is a once-daily, two-week therapy in development for the treatment of MDD and postpartum depression. The phase 3 open-label study is evaluating the safety and tolerability of the 30 mg and 50 mg doses in adults aged 18-75 years who have MDD and a baseline total score of ≥20 on the Hamilton Rating Scale for Depression (HAMD-17).
In patients who received a 14-day course of zuranolone 30 mg, the need for additional courses was assessed according to scores on the HAMD-17 and the Patient Health Questionnaire (PHQ-9). Patients could receive up to 5 treatments over the 12-month study period, with at least 56 days between courses.
The newly released data show zuranolone (SAGE-217) was “generally well-tolerated” in both dose cohorts, and adverse events were “generally consistent” with results from previous zuranolone trials, according to a press release from Sage.
In the 30 mg cohort, the most common treatment emergent adverse events were headache (14.2%), somnolence (11.9%), and dizziness (7.4%). In the 50 mg cohort, somnolence, dizziness, and sedation were observed to be more frequent, but were similar in severity as in the 30 mg group. Most adverse events in both groups were mild or moderate, Sage reported.
The analysis also found that patients who had a decrease of ≥50% in their HAMD-17 baseline score after their initial 14-day course of zuranolone 30 mg required a mean of 2.2 treatments over the 12-month study. Among the 489 patients who responded to the initial 30 mg treatment and stayed in the study, 210 (42.9%) patients used only the single first course, 125 (25.6%) used a total of 2 courses, 58 (11.9%) used a total of 3, 53 (10.8%) used a total of 4, and 43 (8.8%) used a total of 5.
Sage plans to report more data on the 50 mg dose cohort in late 2021.
Sage is developing zuranolone in the United States with Biogen and the companies will market the drug together if development efforts are successful and it is approved by the US Food & Drug Administration (FDA). The FDA has previously granted zuranolone the Breakthrough Therapy Designation.
Zuranolone’s pharmacology is similar to that of the intravenous drug brexanolone (Zulresso), which was approved by the FDA in 2019 for the treatment of postpartum depression.
Sage Therapeutics announces continued positive zuranolone data for both 30 mg and 50 mg doses in open-label SHORELINE study in patients with MDD [press release]. Cambridge, MA: Sage Therapeutics; March 17, 2021.