• by Thom Forbes  @tforbes, March 20, 2019

The Food and Drug Administration yesterday approved the use of Sage Therapeutics’ Zulresso, an intravenous treatment for postpartum depression (PPD) that must be administered by a health care provider in a certified health care facility. The proprietary formulation of brexanolone can cost as much as $34,000, plus the price of a hospital stay, over the course of the two-and-a-half days (60 hours) of treatment.

“Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond,” says Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research, in the FDA’s release announcing the decision.

“The drug works very quickly, within 48 hours -- a significant improvement over currently available antidepressants, which can take two to four weeks to have an effect, if they work at all,” writes Pam Belluck for the New York Times. “Experts say the new treatment will provide immediate relief for mothers whose depression keeps them from providing their babies with the care, bonding and nurturing that is crucial for healthy development.”

“The Centers for Disease Control and Prevention estimates that postpartum depression nationally impacts one in nine women,” Joel Shannon reports for USA Today. That’s about 400,000 women annually.

“Currently, postpartum depression is treated with counseling and medication that can take weeks to work, The National Institute of Mental Health says. Untreated postpartum  depression can last for months or years, NIMH says,” Shannon adds.

“One of the difficulties with psychiatric illness is that we often don’t know what causes it or why someone becomes ill,” Dr. Lucy Puryear, medical director of The Women’s Place, Center for Reproductive Psychiatry at Texas Children’s Pavilion for Women, tells Stat’s Adam Feuerstein. “With postpartum depression, having an illness that is most likely linked to a hormonal trigger and can be treated with a hormonal therapy like [Zulresso] goes a long way toward decreasing stigma, increasing acceptance of the diagnosis, and encouraging women to seek help.”

“Samantha Meltzer-Brody, a psychiatrist at the University of North Carolina at Chapel Hill, who led the clinical trials for the drug, said the medication is such an improvement over current therapies that she doubts the IV administration will discourage its use. She noted that postpartum depression, one of the most common complications of childbirth, is ‘underdiagnosed and neglected,’ and that suicide is a major cause of maternal death,” Laurie McGinley and Lenny Bernstein report for the Washington Post.

“For women suffering, you can say, ‘You can come in and be treated and in 2.5 days it can go away, and not come back," Meltzer-Brody tells them.

The clinical trials “involved 247 women randomly selected to receive a placebo or brexanolone -- a relatively small number of participants, compared to many other medical trials. Still, the results were considered persuasive by a joint FDA advisory committee last year, which recommended approval in near-unanimous votes,” the NYT’s Belluck reports.

In the two two phase III studies, “some of the women were given 60-hour IV infusions of smaller or larger doses of brexanolone while others were given a placebo.The researchers found that the women who received brexanolone infusions had ‘significant and clinically meaningful’ reductions in their depression scores,” CNN’s Jacqueline Howard writes.

“In the first study, by the end of 60 hours, the average reduction was 19.5 points in the brexanolone group that received smaller doses, and 17.7 points in the brexanolone group that received larger doses, compared with 14 points in the placebo group. In the second study, which had only one brexanolone group, the average reduction in score was by 14.6 points in the brexanolone group compared with 12.1 points in the placebo group at 60 hours, the researchers found,” Howard continues.

“Overall, at 60 hours, about 75% of women who received brexanolone were at least 50% improved in their symptoms and about half of women who received brexanolone were no longer clinically depressed,” a researcher involved in two of the drug's clinical trials tells Howard.

Sage CEO Jeff Jonas “expects wide reimbursement for Zulresso, based on talks the company has already had with insurance companies. The most significant commercial challenge, Jonas adds, will be helping hospitals prepare and train staff to administer the drug,” Stat’s Feuerstein writes.