FDA approves ZULRESSO™ (brexanolone) injection for postpartum depression

CHAPEL HILL, NC – The U.S. Food and Drug Administration (FDA) approved ZULRESSO (brexanolone) injection today for the treatment of postpartum depression (PPD) after reviewing the results from three multicenter, randomized, double-blind, parallel-group, placebo-controlled trials in the U.S. Results from the placebo controlled, double blind trials with ZULRESSO were previously published in two articles in The Lancet. UNC School of Medicine (SOM) researcher Samantha Meltzer-Brody, MD, MPH, was the academic principal investigator of the trials, and says this approval could change the way postpartum depression is treated.

“FDA approval of a drug that was developed specifically for postpartum depression is a game-changer for women’s health,” said Meltzer-Brody, director of Perinatal Psychiatry Program at the UNC SOM and the Ray M. Hayworth Distinguished Professor in Mood and Anxiety Disorders. “Given the results of the ZULRESSO clinical trials, we believe that this will be an important treatment option which could provide relief for women with PPD, a disorder with a range of postpartum severity.”

ZULRESSO will be administered to patients under a Risk Evaluation and Mitigation Strategy (REMS) in a medically supervised healthcare setting that provides monitoring to mitigate the risk of serious harm resulting from excessive sedation and sudden loss of consciousness during the ZULRESSO infusion.

Brexanolone works differently than existing anti-depressant medications. Given its approval by the FDA, it is the first drug specifically indicated for PPD. Common symptoms of PPD – a mood disorder in women that can be triggered by fluctuations in reproductive hormones – include low mood, feeling overwhelmed, anxious and ruminating thoughts, potential withdrawal from the baby and her family, and suicidal thoughts in the most severe cases. PPD is one of the most common complications of pregnancy, with one in nine mothers in the U.S. experiencing it.

“With current anti-depressant SSRIs (selective serotonin reuptake inhibitors) it could take four to six weeks to get a treatment response,” said Meltzer-Brody. “The weeks and months following birth are a critical period for mother-infant bonding, so finding a quick-acting treatment is crucial for both mom and baby. In the trials with ZULRESSO, we saw patients starting to feel better within days.”

ZULRESSO is an allosteric modulator of both synaptic and extra-synaptic GABA? receptors. The GABA pathway may play a key role in regulating hormones that researchers believe can lead to PPD.

An integrated analysis of results from the three double-blind, placebo-controlled trials of ZULRESSO was published in The Lancet in August 2018. The trials took place at 30 sites in the U.S., including UNC’s Perinatal Psychiatry Unit, which was the first and only site to initially administer the drug in the open label trial and participated in the full clinical trial program. Eligible trial participants included women age 18-45 years old who were six months postpartum or less at screening and had onset of symptoms during pregnancy or within 4 weeks of delivery. They also had to be experiencing moderate to severe postpartum depression, which was assessed by the Hamilton Depression Rating Scale (HAM-D).

The integrated analysis published most recently in The Lancet looked at results of the trials which randomized 209 women to receive a double-blinded 60-hour infusion of either ZULRESSO 90 μg/kg/hr or placebo. A unique dose group of ZULRESSO 60 μg/kg/hr in one of the studies was not included in the integrated efficacy analysis, but was included in integrated analyses of safety. Brexanolone injection 90 μg/kg/hr was administered to 102 women with moderate or severe PPD who also were evaluated throughout the infusion, after the infusion stopped and then periodically for up to 30 days. Another 107 women were administered a placebo and evaluated during the same timeframe. The first statistically significant reduction in depression severity with brexanolone injection relative to placebo was observed as early as 24 hours after dosing. At the end of the 60-hour infusion, the average reduction in patients’ Hamilton Rating Scale for Depression (HAM-D or depression severity score) was 17.0 points for women in the brexanolone injection 90 μg/kg/hr group, versus 12.8 in the placebo group (p

The most common adverse events in the ZULRESSO clinical studies were sedation/somnolence, dizziness, dry mouth, flushing and loss of consciousness.

David Rubinow, MD, chair of the Department of Psychiatry at the UNC SOM and one of the coauthors of the published results, says, “As long as I’ve been in this field, I don’t believe I’ve ever seen results quite as dramatic as those from this program.”

“This is a very different model for how we treat depression,” Meltzer-Brody said. “Having a drug approved to treat PPD that works quickly and effectively, yet is also durable, is a huge step forward for psychiatry in general.”

###