A Sage Therapeutics drug developed to treat postpartum depression has won FDA approval, making it the first oral therapy for the disorder. But it’s a mixed regulatory outcome for the drug, which failed to secure an additional nod in major depressive disorder.
The Sage drug, known in development as zuranolone, will be marketed for postpartum depression under the name Zurzuvae.
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Cambridge, Massachusetts-based Sage already had a postpartum depression drug. Zulresso was approved by the FDA in 2019. But that drug is administered as a 60-hour continuous infusion, which poses a burden to patients. Zurzuvae is a small molecule formulated as a once-daily pill. The new Sage drug is also fast acting, offering an onset of effect within days compared to the weeks many depression drugs need to start showing an effect.
Like Zulresso, Zurzuvae targets the GABA system, a signaling pathway of the central nervous system that contributes to the regulation of brain function. The drug is what’s called a positive allosteric modulator of GABA-A receptors. Patients take Zurzuvae once daily in a treatment course that lasts 14 days.
FDA approval of Zurzuvae is based on results from two placebo-controlled studies enrolling women with postpartum depression. These participants met the criteria for a major depressive episode and they had symptoms that began in the third trimester or within four weeks of delivery. The main goal of both studies was to show a change in score at day 15 according to a scale used to assess depression symptoms. In both groups, results showed significantly greater symptom improvement in the treatment cohorts compared to the placebo arms. The drug also showed durability with an effect that was maintained for four weeks.
“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness—even, in severe cases, thoughts of harming themselves or their child,” Tiffany Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, said in agency’s approval announcement. “And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development. Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”
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The most common side effects of Zurzuvae include drowsiness, dizziness, diarrhea, fatigue, cold symptoms, and urinary tract infection. Zurzuvae’s label carries a black box warning that cautions patients that the drug may impair their ability to drive and perform other activities. The FDA advises that patients do not drive or operate heavy machinery for at least 12 hours after taking the drug.
Zurzuvae comes from the labs of Sage, but it will be commercialized under a partnership with Biogen, which has its own stable of neuroscience drugs. In 2020, Biogen began an alliance on Zurzuvae, committing more than $1.5 billion in an upfront payment and equity investment. The deal put Sage in line for up to $1.6 billion in milestone payments. In addition to sharing in the development of the drug, both companies will share equally in the profits and losses from its commercialization in the U.S. Biogen is responsible for developing and commercializing Zurzuvae outside the U.S., except for Japan, Taiwan, and South Korea.
Sage has touted Zurzuvae as a potential treatment for many psychiatric conditions. Postpartum depression and major depressive disorder are the first two indications in which the biotech tested the drug. In 2019, Zurzuvae failed to achieve the main goal of a pivotal study in major depressive disorder. With FDA permission, the company tried again with a slate of three studies. Results reported in 2021 showed an effect in the treatment arm that was enough to be statistically significant. But durability was questionable, as the results also suggested a waning of effect after day 3 of treatment.
[Update: The following two paragraphs added with comment from Sage.] In a statement issued late Friday, Sage said the FDA complete response letter for the drug in major depressive disorder stated that the application did not contain substantial evidence of effectiveness and additional clinical testing is needed. The company added that it’s reviewing the feedback with Biogen and evaluating the next steps in that indication.
Zurzuvae’s positive Phase 3 results in postpartum depression were reported last summer. Sage said Friday that it expects to launch the drug in the fourth quarter of this year following scheduling by the U.S. Drug Enforcement Administration. Zuranolone, the active pharmaceutical ingredient in the product, has the potential for abuse and misuse. Sage said DEA review of Zurzuvae is expected within 90 days.
Despite winning the first FDA approval of a postpartum depression drug, Sage has not made a big splash in that indication. Zulresso accounted for just $7.6 million in sales in 2022, according to Sage’s annual report. While Zurzuvae gives Sage and partner Biogen the opportunity to grow in the postpartum depression market, some of the new product’s sales will likely come at the expense of the old one.
Photo: kieferpix, Getty Images
