Zuranolone Eases MDD for Majority of Study Participants, Interim Analysis Shows

An interim analysis of a phase 3, open-label, year-long study evaluating episodic treatment with zuranolone for major depressive disorder (MDD) found the majority of patients at study exit had minimal or mild depressive symptoms, including those who left the study early. Researchers presented their findings today in a poster presentation at the 35th Annual Psych Congress in New Orleans, Louisiana.

“Zuranolone is an investigational neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic GABA receptors in clinical development as an oral, once-daily, 14-day treatment course for adults with MDD,” wrote presenter Andrew Czysz.

The ongoing SHORELINE study includes adults with MDD and a Hamilton Rating Scale for Depression (HAMD-17) total score of 20 or higher. Participants who respond at day 15 have the option to continue the study. Participants with a follow-up score of 20 or higher on the HAMD-17 are eligible for repeat treatment 56 days after the initial 14-day treatment or at day 70.

Of all 924 patients in the interim analysis, 22.5% did not respond to the initial 14-day treatment, 33.4% withdrew early from the study, and 44% completed the study.

Among participants who responded to the initial 14-day treatment and completed the study, the overall mean ± standard deviation (SD) HAMD-17 score was 8.6 ± 7.1. By dosage, the mean ± SD HAMD-17 score was 9.1±7.1 with zuranolone 30 mg and 6.7 ± 6.8 with zuranolone 50 mg. The median time since the start of the last treatment was 210.5 days overall, 183.0 days with zuranolone 30 mg, and 295 days with zuranolone 50 mg.

For participants who responded to the initial treatment but who discontinued the study after day 28, the mean ± SD HAMD-17 score was 11.2 ± 7.3 overall, 11.3 ± 7.1 with zuranolone 30 mg, and 10.9 ± 8.0 with zuranolone 50 mg. The median time since the start of the last treatment was 94 days overall, 84.5 days with zuranolone 30 mg, and 131 days with zuranolone 50 mg among responders who discontinued.

Depressive symptoms at study exit were minimal or mild for most patients. Among patients who completed the study, 76.8% overall had minimal or mild depressive symptoms, 75.2% with zuranolone 30 mg, and 82.1% with zuranolone 50 mg. Among participants who withdrew early, 59.4% overall had minimal or mild symptoms, 57.9% with zuranolone 30 mg, and 64.7% with zuranolone 50 mg at study exit.

“Most patients who discontinued withdrew consent or were lost to follow-up and exited >90 days (median) since the start of their last zuranolone treatment, suggesting few patients left after an ineffective/poorly tolerated 14-day treatment,” researchers wrote.

Sage Therapeutics Inc. and Biogen Inc. sponsored the study.

Reference

Czysz A, et al. Depressive symptom severity in patients with major depressive disorder (MDD) at study exit in the one-year SHORELINE study of episodic treatment with zuranolone. Poster presented at Psych Congress; September 17-20, 2022; New Orleans, Louisiana.