Zuranolone

• Sage Therapeutics, Inc. (Nasdaq: SAGE) today reported business highlights and financial results for the third quarter ended September 30, 2023.
• ZURZUVAE is being developed and commercialized in collaboration with Biogen Inc. Sage also commercializes ZULRESSO® (brexanolone) CIV injection in the treatment of PPD.
• Restructuring Expenses: Restructuring expenses were $33.6 million in the third quarter of 2023 due to the August 2023 corporate reorganization.
• ET to review its third quarter 2023 financial results and discuss recent corporate updates.

• While mothers with postpartum depression have always faced barriers accessing the care they need, things have been particularly bad since the onset of the COVID-19 pandemic.
• However, the pandemic also coincided with a period of significant innovation in treatment that may increase access to and effectiveness of care.

Medications specifically for PPD

• It represented the first of an entirely new class of medicines for postpardum depression (PPD), which target the steep decrease in hormones after delivery.
• Brexanolone is a synthetic version of allopregnanolone, a naturally occurring substance made from progesterone, that helps the brain regulate stress.
• Its approval in the U.S. was especially notable for two reasons: it was the first medicine approved specifically for the treatment of PPD, and it takes effect especially quickly — within 60 hours.
• Early studies of zuranolone suggest PPD symptom improvement can be observed as early as three days after starting the treatment.

Behind the hype

• If approved in Canada, it would also add to the array of effective treatments that already exist.
• These include evidence-based talking therapies like cognitive behavioural therapy and interpersonal psychotherapy, which are first-line treatments for mild to moderate PPD.
• Antidepressant medications like the selective serotonin re-uptake inhibitors (SSRIS, such as sertraline and escitalopram) are also widely available and usually recommended as second-line therapies for most individuals with PPD.
• Only individuals with more severe depression that emerged between the third trimester of pregnancy and four weeks post-delivery could be enrolled.

PPD is still underdiagnosed

• However, it is important in this case that we not lose sight of the fact that PPD is a vastly underdetected and undertreated problem for which safe and effective treatments already exist.
• Research into treatments for PPD and the federal government’s actions in appointing a Minister of Mental Health and Addictions and prioritizing perinatal parents are also cause for genuine optimism.
• While zuranolone is raising awareness about PPD, it’s important to highlight the need to develop national quality standards and Canadian-specific stepped-care models and care pathways.

• View the full release here: https://www.businesswire.com/news/home/20230807136425/en/
  The national clinical trials for zuranolone were led by the Feinstein Institutes for Medical Research at Northwell Health.
• “After years of dedicated research and collaboration with other scientists, women living with postpartum depression have a new, at-home, 14-day treatment option that has the potential to alleviate their symptoms,” said Dr. Deligiannidis.
• Deligiannidis is a leader in clinical trials for postpartum depression, a condition that affects millions,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes, Karches Family Distinguished Chair in Medical Research.
• “The FDA approval stemming from her work will make available new therapeutic options that are clearly needed.”
  The Feinstein Institutes and Dr. Deligiannidis lead in researching new methods to diagnose and treat perinatal depression.

• Fourteen-day oral, at-home, treatment with zuranolone versus placebo resulted in statistically significant improvement in depressive symptoms, as measured by change from baseline in HAMD-17 total score.
• Results showed that 57 percent of the women taking zuranolone versus 38 percent of women taking placebo experienced a 50 percent or more improvement in their depressive symptoms at day 15.
• The trial demonstrated the improvement in depressive symptoms with zuranolone at 30 mg versus placebo in patients with PPD and that zuranolone was generally well tolerated.
• The SKYLARK and ROBIN clinical trials provide some of the most substantial results for improving depressive symptoms in women with PPD.