Zuranolone Co-Initiated With Antidepressant Rapidly Drops Depressive Symptoms

When co-initiated with an antidepressant, the investigational drug zuranolone significantly reduced depressive symptoms in patients with major depressive disorder within 3 days compared with placebo co-initiated with an antidepressant, drugmakers Sage Therapeutics and Biogen announced.

The phase 3, double-blind CORAL Study randomized 440 patients with major depressive disorder to treatment with zuranolone 50 mg co-initiated with an open-label, standard-of-care antidepressant (clinician-chosen sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine) or placebo co-initiated with an open-label antidepressant once a night for 14 days.

Zuranolone achieved both the study’s primary and key secondary endpoints, according to results reported by Sage Therapeutics and Biogen. The primary endpoint was a statistically significant drop in depressive symptoms on day 3: mean changes from baseline on the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score were ­­-8.9 ± 0.39 for people in the antidepressant-plus-zuranolone group compared with -7.0 ± 0.38 for people in the antidepressant-plus-placebo group.

The key secondary endpoint was the treatment effect over the 2-week treatment period. Mean changes over the 2 weeks in the antidepressant-plus-zuranolone group were -11.7 ± 0.40 compared with -10.1 ± 0.39 for people in the antidepressant-plus-placebo group. Other secondary endpoints showed a statistically significant drop in HAMD-17 score in the antidepressant-plus-zuranolone group compared with the antidepressant-plus-placebo arm on days 8 and 12. Day 15 demonstrated numerical superiority with zuranolone, while day 42 showed equivalence.

Related: Patients With MDD Show Rapid Symptom Improvement With Investigational Drug Zuranolone

In a subgroup of patients with major depressive disorder and elevated anxiety, a population historically less responsive to antidepressants, zuranolone co-initiated with an antidepressant was nominally statistically significant to placebo in reducing depressive symptoms, the drugmakers reported.

Zuranolone co-initiated with an antidepressant was generally well-tolerated in the trial. Most treatment-emergent adverse events were mild or moderate, and no new safety signals were identified.

“Including the CORAL Study, zuranolone now has 6 positive clinical studies,” said Sage chief executive officer Barry Greene, “and we remain on track to start the rolling submission for a new drug application in major depressive disorder early this year, with completion targeted for the second half of 2022.”

Reference

Sage Therapeutics and Biogen announce the phase 3 CORAL Study met its primary and key secondary endpoints - comparing zuranolone 50 mg co-initiated with standard of care antidepressant vs. standard of care co-initiated with placebo in people with MDD. News release. Sage Therapeutics Inc. and Biogen Inc. February 16, 2022. Accessed February 25, 2022.