A phase 3 study evaluating zuranolone in women with postpartum depression met its primary and key secondary endpoints, according to Sage Therapeutics and Biogen.
Zuranolone is an investigational oral neuroactive steroid GABA-A receptor positive allosteric modulator. The SKYLARK study (ClinicalTrials.gov Identifier: NCT04442503) assessed the efficacy and safety of zuranolone compared with placebo in adult women with severe postpartum depression. Patients were randomly assigned to receive either zuranolone 50mg (n=98) or placebo (n=97) orally once nightly for 14 days. The primary endpoint was the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at day 15.
Findings showed that treatment with zuranolone led to a statistically significant and clinically meaningful improvement in depressive symptoms. The least-squares (LS) mean (SE) change from baseline in HAMD-17 total score at day 15 for women who received zuranolone was -15.6 (0.82) vs -11.6 (0.82) for placebo (LS mean difference, -4.0 points; P =.0007). Statistically significant improvements in depressive symptoms were observed as early as day 3 and sustained through day 45.
Zuranolone was also associated with a statistically significant improvement in the Clinical Global Impression Severity (CGI-S) scale at day 15 (secondary endpoint), compared with placebo (-2.2 vs -1.6, respectively; P =.0052).
The most common treatment emergent adverse events reported were somnolence, dizziness, sedation, headache, diarrhea, nausea, urinary tract infection, and COVID-19. There were no reports of withdrawal symptoms or increased suicidal ideation or behavior among study participants.
Results from SKYLARK complement those from the phase 3 ROBIN study (ClinicalTrials.gov Identifier: NCT02978326), which evaluated the efficacy, safety, and pharmacokinetics of a 30mg dose of zuranolone in the treatment of postpartum depression.
The New Drug Application submission for zuranolone for postpartum depression is expected in early 2023.
Sage Therapeutics and Biogen announce that the phase 3 SKYLARK study of zuranolone in postpartum depression met its primary and all key secondary endpoints. News release. Sage Therapeutics and Biogen Inc. Accessed June 1, 2022. https://www.businesswire.com/news/home/20220531006081/en/Sage-Therapeutics-and-Biogen-Announce-that-the-Phase-3-SKYLARK-Study-of-Zuranolone-in-Postpartum-Depression-Met-its-Primary-and-All-Key-Secondary-Endpoints