FDA Approves Zuranolone for Postpartum Depression

The US Food and Drug Administration (FDA) has approved zuranolone for the treatment of postpartum depression (PPD) in adult patients.¹

The indication granted to Biogen Inc and Sage Therapeutics introduces a potentially faster-acting, once-daily oral therapy to the depression market, as the neuroactive steroid GABA-A receptor positive allosteric modulator targets the major inhibitor signaling pathway of the brain and central nervous system over just a 14-day regimen.

It marks zuranolone as the first drug approved to treat PPD.

In pivotal phase 3 data from the LANDSCAPE and NEST programs supporting the FDA approval, zuranolone was associated with rapid-onset benefit in 17-item Hamilton Depression Rating Scale (HAMD-17) versus placebo in patients with major depressive disorder (MDD) at day 3,² and in women with PPD at day 15.³

In phase 2 and 3 clinical trial open-label extension data presented at the American Psychiatric Association (APA) 2022 Annual Meeting in New Orleans, investigators shared findings showing patients with either MDD or PPD benefitted from zuranolone per HAMD-17 through 1 year post-initiation.

In an interview with HCPLive this week, zuranolone investigator Anita Clayton, MD, Wilford W. Spradlin Professor and Chair of the department of psychiatry & neurobehavioral sciences, and professor of clinical obstetrics & gynecology at the University of Virginia School of Medicine, discussed the unique mechanism of action and method of delivery that makes the agent a viable option for depressive disorders.

“It’s not like our standard of care, acting on monoamines like dopamine, serotonin and norepinephrine,” Clayton said. “It provides an opportunity for it to act rapidly, to maintain effect after the completion of a 14-day course, and it’s well tolerated during that period of time.”

“This is something that’s a completely different paradigm,” Clayton continued. “People do not need to continue taking this medication beyond the 14-day course.”

Clayton highlighted long-term maintenance of effect data showing >70% of initially treated patients maintained clinical response for more than a year. Another 50% at the 50 mg dose were reporting sustained clinical benefit without any other therapy; 30% required a secondary course of zuranolone, and 20% required ≥3 courses.

“What it says is that with 1 or potentially 2 doses over the course of a year, about 80% of responders stay well,” Clayton said. “This is just completely different—you don’t have to be on chronic daily dosing, and you don’t have the chronic adverse effects of the standard-care antidepressants.”

During a prior interview with HCPLive at APA 2022, Clayton described depression pharmaceuticals as a field with few advancements in the last 20 years. Speaking on that thought this week, Clayton clarified that psychiatry’s most prominent advances in that time have focused on treatment-resistant depression. What zuranolone provides is a more encompassing and assuring option for patients who may have failed iterations of other antidepressant regimens.

In an HCPLive Peer Exchange panel discussion earlier this year, Sagar V. Parikh, MD, John F. Greden Professor of Depression and Clinical Neuroscience at discussed the benefit zuranolone may play in even expediting the progression of benefit patients with MDD or PPD are hoping to eventually achieve with standard antidepressant regimens.⁵

“In a way, you satisfy everybody because the low and slow people are like, ‘I don’t know, I don’t want to give up the traditional time-honored medicines’,” Parikh explained. “Okay. So, stay on it, or start a standard older treatment, but to jumpstart your improvement, you can benefit by adding some zuranolone as well.”

Andrew J. Cutler, MD, a psychiatrist with Beth Israel Lahey Health, Mount Auburn Hospital, echoed Parikh’s sentiment on the panel.

“It’s very interesting here that we’re talking about not only a more rapid-acting paradigm here with zuranolone, we’re also talking about this episodic treatment paradigm,” Cutler said. “And it’s theoretically possible, isn’t it?”

References

1. ^{FDA. FDA Approves First Oral Treatment for Postpartum Depression. Press release. Published August 4, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression}
2. ^{Kuntz L. Zuranolone: New Data Presented at American College of Neuropsychopharmacology Congress. Psychiatric Times. Published December 15, 2021. https://www.psychiatrictimes.com/view/zuranolone-new-data-presented-at-american-college-of-neuropsychopharmacology-congress}
3. ^{Sage Therapeutics. Sage Therapeutics and Biogen Announce that the Phase 3 SKYLARK Study of Zuranolone in Postpartum Depression Met its Primary and All Key Secondary Endpoints. Press release. Published June 1, 2022. https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-phase-3-skylark-study}
4. ^{Kunzmann K. Zuranolone Benefits Major Depression, Postpartum Depression in Clinical Program. HCPLive. Published May 22, 2022. https://www.hcplive.com/view/zuranalone-benefits-major-depression-postpartum-depression-clinical-program}
5. ^{Cutler A, Mattingly G, Parikh S. Clinical Data on Zuranolone Use in MDD. HCPLive. Published January 20, 2023. https://www.hcplive.com/view/clinical-data-on-zuranolone-use-in-mdd}