麻豆传媒

An oral GABA-active agent reduced symptoms for women with postpartum depression in a phase III trial sponsored by the drugmaker, researchers said.

Among 151 women diagnosed with postpartum depression who were at most 6 months' postpartum, those on 30-mg daily zuranolone -- with a mechanism similar to the intravenous drug brexanolone (Zulresso) -- had significantly improved symptoms from baseline compared with placebo at 14 days, measured through the Hamilton Rating Scale for Depression (HAMD-17), reported Samantha Meltzer-Brody, MD, MPH, director of the University of North Carolina Center for Women's Mood Disorders in Chapel Hill, and colleagues.

The proportion of women on zuranolone who responded to treatment, measured through a reduction in HAMD-17 scores by at least 50%, was also higher than the placebo group at day 8 (65% vs 45%, P=0.0127) and day 15 (72% vs 48%, P=0.0049), Meltzer-Brody reported in a virtual poster session at the

Remission rates, defined as total HAMD-17 scores of 7 or less, were also significantly higher in the zuranolone versus placebo group at day 8 (32% vs 19%, P=0.0200) and day 15 (45% vs 23%, P=0.0110), she noted.

"To see a clinically significant improvement in two weeks is unlike other antidepressants on the market, which generally take a month or longer to work," Meltzer-Brody told 麻豆传媒. "The postpartum period is a time that is so vulnerable, so something that has rapid onset of action is so important in order to get mom better quickly so you're making sure you're not having disruption with mom-baby attachment and everything else."

Her poster also included data on brexanolone, but it was compared only to placebo, not directly to zuranolone. However, the treatment effects of both drugs relative to placebo appeared generally similar.

The proportion of women experiencing a major depressive episode after delivery ranges between 10-15% and is even higher among women with a history of depression, between 25% and 40%, noted Marlene P. Freeman, MD, of Massachusetts General Hospital in Boston, in a separate Psych Congress presentation on postpartum mood disorders.

Freeman, who is participating in zuranolone research, said that this new class of rapid-acting antidepressants is exciting and that having an oral compound available would further improve treatment options for women with postpartum depression.

Zuranolone, formerly known as SAGE-217, is an oral neuroactive steroid that flopped late last year in a trial for major depressive disorder. But sponsor Sage Therapeutics thought the drug still had promise and decided to .

The FDA approved Sage's brexanolone, an endogenous neuroactive steroid, in an intravenous formulation in 2019. Both brexanolone and zuranolone are allosteric modulators that bind to synaptic and extrasynaptic GABA_a receptors.

In another analysis of the same cohort presented at the Psych Congress -- this one measuring treatment response through the Edinburgh Postnatal Depression Scale (EPDS) -- women on zuranolone also had significantly greater symptom improvement from baseline compared with placebo, reported Ming-Yi Huang, PhD, of Sage Therapeutics in Cambridge, Massachusetts.

At day 45, the number needed to treat for remission was 5 using the least strict definition of remission (EPDS <13), Huang reported. The number needed to treat for remission defined by EPDS scores under 10 and EPDS scores under 7 were both 4, she added.

"This analysis primarily focused on the day 45 time point, as patient rated scales may require more time to observe changes in depressive symptoms relative to physician rated scales," Huang said in an oral presentation of her poster.

For the so-called Robin study, adult women under 45 years with HAMD-17 scores of at least 26 were included. Women were enrolled if they had the onset of a major depressive episode in their third trimester or up to 4 weeks' postpartum.

Zuranolone was associated with significant symptom improvement by day 3 (P=0.0252), which was maintained at all time points through the end of follow-up at day 45 (P=0.0216), researchers reported.

Adverse events associated with treatment included drowsiness and sedation, headache, dizziness, and upper respiratory tract infection. Three patients in both the placebo and zuranolone groups experienced a serious adverse event, the authors reported. However, no increase in suicidality was observed with treatment, they added.

The drugmaker said topline results from another trial testing 50-mg zuranolone versus placebo