EPV1301 - Post-Hoc Analysis of Zuranolone Efficacy and Safety by Baseline MADRS Depressive Symptom Severity in SKYLARK and ROBIN
EPV1301
Post-Hoc Analysis of Zuranolone Efficacy and Safety by Baseline MADRS Depressive Symptom Severity in SKYLARK and ROBIN
K. M. Deligiannidis 1, J. A. Ramos-Quiroga 2, B. Nair 3, A. Artemyeva 4, K. LaGuerre 4, H. Finnigan 4, F. Forrestal 4, J. Jung 4, V. Nguyen 4, M. Adams 4,*
1Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, United States, 2Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 3Kent and Medway Mental Health NHS Trust, Maidstone, United Kingdom, 4Biogen Inc., Cambridge, United States
Introduction: Postpartum depression (PPD) is a common perinatal condition with significant consequences for the patient, child, and family. The efficacy and safety of zuranolone, an oral, once-daily, 14-day treatment for PPD in adults, was assessed in the pivotal SKYLARK and ROBIN studies. The Hamilton Depression Rating Scale 17 (HAMD-17) and Montgomery-Asberg Depression Rating Scale (MADRS) were the primary and a secondary endpoint, respectively. Both studies enrolled participants with a HAMD-17 score ≥ 26 (indicative of severe depressive symptoms). However, the efficacy and safety of zuranolone in patients with moderate PPD remains uncertain.
Objectives: This post-hoc analysis of SKYLARK and ROBIN aimed to characterize the efficacy and safety of zuranolone in patients with PPD with moderate or severe depressive symptoms defined by baseline MADRS score.
Methods: Two severity subgroups were defined based on baseline MADRS total score: moderate (20-34) and severe (≥ 35) depressive symptoms. Changes from baseline (CFB) in HAMD-17 and in MADRS total scores were analyzed in each subgroup using a mixed-effects model for repeated measures. Treatment-emergent adverse events were evaluated by subgroup.
Results: Both SKYLARK and ROBIN showed similar demographic and baseline characteristics in the moderate and severe subgroups, with a balanced distribution of moderate and severe MADRS scores. In each study, the least squares mean (LSM) treatment differences in CFB in HAMD-17 and MADRS total scores for each subgroup favored zuranolone at Day 15, with effects sustained to Day 45 (Tables 1 and 2). No clinically meaningful differences in safety were observed across the subgroups in either study.
Tables 1 and 2: LSM Treatment Differences in CFB versus placebo in HAMD-17 and MADRS Total Scores at Days 15 and 45
SKYLARK |
HAMD-17 |
p-value |
MADRS |
p-value |
|
Day 15 | ||||
|
Moderate |
-4.4 (n=87) |
0.005 |
-5.2 (n=87) |
0.02 |
|
Severe |
-4.0 (n=95) |
0.03 |
-5.0 (n=94) |
0.06 |
|
Day 45 | ||||
|
Moderate |
-3.8 (n=80) |
0.03 |
-4.5 (n=80) |
0.05 |
|
Severe |
-3.4 (n=88) |
0.08 |
-5.0 (n=88) |
0.08 |
ROBIN |
HAMD-17 |
p-value |
MADRS |
p-value |
|
Day 15 | ||||
|
Moderate |
-3.2 (n=60) |
0.09 |
-3.1 (n=60) |
0.20 |
|
Severe |
-4.6 (n=87) |
0.02 |
-5.7 (n=87) |
0.04 |
|
Day 45 | ||||
|
Moderate |
-3.6 (n=58) |
0.06 |
-4.6 (n=58) |
0.06 |
|
Severe |
-4.3 (n=84) |
0.02 |
-7.1 (n=84) |
0.01 |
Conclusions: Post hoc analyses suggested that the clinical effects of zuranolone treatment versus placebo could be applied to patients with moderate or severe depressive symptoms.
Disclosure of Interest: K. Deligiannidis Consultant of: GH Research, Sage Therapeutics, Inc., Brii Biosciences, Inc., Lipocine, Gerbera Therapeutics, Reunion Neuroscience, Neurocentria, Brainify, and NextSense, J. A. Ramos-Quiroga Grant / Research support from: Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Exeltis, Idorsia, Casen-Recordati, Takeda, Neuraxpharm, Oryzon, Roche, Probitas, Rubió, and Johnson & Johnson., Consultant of: Biogen, Idorsia, Casen-Recordati, Johnson & Johnson, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, Lilly, BMS, Medice, Rubió, Uriach, Technofarma, and Raffo, Speakers bureau of: Biogen, Idorsia, Casen-Recordati, Johnson & Johnson, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, Lilly, BMS, Medice, Rubió, Uriach, Technofarma, and Raffo, B. Nair: None Declared, A. Artemyeva Employee of: Biogen Inc. and may hold stock, K. LaGuerre Employee of: Biogen Inc. and may hold stock, H. Finnigan Employee of: Biogen Inc. and may hold stock, F. Forrestal Employee of: Biogen Inc. and may hold stock, J. Jung Employee of: Biogen Inc. and may hold stock, V. Nguyen Employee of: Biogen Inc. and may hold stock, M. Adams Employee of: Biogen Inc. and may hold stock