FDA Accepts New Drug Application for New Rapid Treatment for Major Depressive Disorder

The FDA accepted a new drug application (NDA) for SAGE-217/BIIB125 (Zuranolone; Biogen and Sage Therapeutics), an investigational 14-day, rapid-acting, once-daily, oral treatment for major depressive disorder (MDD) and postpartum depression (PPD) in adults. The NDA is based on the cumulation of data from 7 studies evaluating SAGE-217/BIIB125 for a variety of clinical endpoints, according to a recent press release.

“Most current approved therapies may take weeks or months to work,” said Laura Gault, MD, PhD, chief medical officer at Sage, in the press release. “We are committed to advancing treatments that could help physicians and patients by addressing depression symptoms quickly.”

SAGE-217/BIIB125 is a neuroactive steroid that functions as a positive allosteric modulator (PAM) to alter the protein activity of gamma-Aminobutyric acid type A (GABA-A) receptors. By targeting these receptors, SAGE-217/BIIB125 may be able to rebalance dysfunctional neuronal networks— which regulate functions including mood, arousal, behavior, and cognition— and reset brain function in patients with depression.

Investigators are studying the efficacy SAGE-217/BIIB125 in the LANDSCAPE and NEST clinical development programs. LANDSCAPE is evaluating SAGE-217/BIIB125 for MDD in 5 clinical studies, including MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL, and NEST evaluated SAGE-217/BIIB125 for PPD in 2 studies, ROBIN and SKYLARK. Further, Shionogi evaluated the drug for patients with MDD in Japan in a phase 2 study.

Worldwide, depression is the leading contributor to disability, with about 21 million US adults experiencing at least 1 major depressive episode in 2020 and an estimated 190 million cases of MDD globally that same year. MDD, a mood disorder that causes depressive symptoms which can lead to social, occupational, and educational impairment, may also cause a loss of pleasure in daily activities that can last for as long as 2 weeks. In 2018, the US economic burden of MDD was estimated at $326 billion.

PPD is a common complication of pregnancy (estimated to affect 1 in 8 women in the United States) that may cause significant functional impairment, depressed mood, disinterest in the newborn, or other symptoms of depression, such as loss of appetite, difficulty sleeping, and motor challenges. Along with MDD, its symptoms can significantly impact quality of life (QoL), functioning, and well-being.

The FDA also granted the NDA priority review, assigning it a Prescription Drug User Fee Act action date of August 5, 2023.

Priya Singhal, MD, MPH, executive vice president, head of development and interim head of research and global safety and regulatory sciences at Biogen, adds that “We see potential for [SAGE-217/BIIB125], if approved, to be a meaningful new option that can help address the serious unmet need faced by the diverse populations struggling with MDD and PPD.”

Reference

Biogen and Sage Therapeutics Announce FDA Accepts Filing of New Drug Application and Grants Priority Review of Zuranolone in the Treatment of Major Depressive Disorder and Postpartum Depression. News Release. February 6, 2023. Accessed February 6, 2023. https://investors.biogen.com/news-releases/news-release-details/biogen-and-sage-therapeutics-announce-fda-accepts-filing-new