Incoming Data: News from Naturalistic MDD Clinical Trial

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Sage Therapeutics announced 2 data sets from the ongoing phase 3 open-label SHORELINE study evaluating zuranolone: complete 12-month data from the 30 mg cohort and interim data from the 50 mg cohort. Zuranolone, a once-daily, 2-week therapy for the treatment of major depressive disorder (MDD) and postpartum depression (PPD), is an investigational oral neuroactive steroid (NAS) GABAA receptor positive allosteric modulator.

“Sage embarked on the LANDSCAPE clinical program to evaluate the safety and efficacy of zuranolone with the ambition of reimagining the treatment for depression with the goal of a rapid-acting, durable, treat-as-needed option in a disease where innovation is lacking and the incidence rate has unfortunately increased exponentially in the last 20 years,” Barry Greene, Chief Executive Officer at Sage Therapeutics, said to the press. “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. Designed as a naturalistic study, these data approximate real-world evidence of use of zuranolone at 30 mg and 50 mg doses. We look forward to the results of the WATERFALL and CORAL Phase 3 pivotal data readouts in MDD this year.”¹

This clinical study was designed to evaluate the safety and tolerability of zuranolone 30 mg and 50 mg in adults for up to 1 year, and the currently analyzed data show that zuranolone was generally well-tolerated in both the 30 mg and 50 mg dose cohorts. Reported adverse events were generally consistent with results seen in previous zuranolone clinical trials; they included somnolence, headache, and dizziness.

In the 30 mg zuranolone cohort, 725 participants with MDD were treated with a first dose of zuranolone 30 mg once nightly for 14 days. Researchers evaluated participant response using the 17-item Hamilton Rating Scale for Depression (HAMD-17). The mean baseline HAM-D score (± SD) at entry was 25.3 ± 4.1 (n=725). Of the 725, 173 participants did not achieve response to the first course and left the study; however, 505 (73.5%) patients achieved response and 276 (40.2%) achieved remission (HAM-D ≤7).

From the initial group, 489 continued beyond the first treatment course. Of the 489, 210 used only the single initial course, 125 used 2 total courses, 58 used 3 total courses, 53 used 4 total courses, and 43 used 5 total courses. It was noted that adverse events decreased in frequency through the first 3 courses and remained stable over the next 2 courses.

From May 2020 onwards, all newly enrolled participants received 50 mg of zuranolone. The achieved response rate for these participants is 149/185 (80.5%), while the achieved remission rate is 80/185 (43.2%). This 50 mg cohort has completed the first course and the 12-month follow-up is expected to be completed in late 2021.

The SHORELINE study, as the first naturalistic, clinical development trial for MDD, is providing realistic insight into the potential use for zuranolone, if it is successfully developed and approved. Sage Therapeutics plans to report additional data from patients in the 50 mg dose cohort in late 2021, and present additional data from the study at conferences and in peer-reviewed journal articles.

Reference

1. Sage Therapeutics announces continued positive zuranolone data for both 30 mg and 50 mg doses in open-label SHORELINE study in patients with MDD. BusinessWire. News release. March 17, 2021. https://www.businesswire.com/news/home/20210317005285/en/Sage-Therapeutics-Announces-Continued-Positive-Zuranolone-Data-for-Both-30-mg-and-50-mg-Doses-in-Open-Label-SHORELINE-Study-in-Patients-with-MDD