Biogen Inc. and Sage Therapeutics made the announcement on Friday (August 4) that Zurzuvae (zuranolone) 50 mg, oral, once-daily, 14-day treatment can provide rapid improvements in depressive symptoms for women with PPD.
It is expected to launch and be commercially available in the fourth quarter of 2023 shortly following scheduling as a controlled substance by the US Drug Enforcement Administration, hopefully within three months.
Additionally, the FDA issued a Complete Response Letter (CRL) for the New Drug Application (NDA) for zuranolone in the treatment of adults with major depressive disorder (MDD). The CRL stated that the application did not provide substantial evidence of effectiveness to support the approval of zuranolone for the treatment of MDD and that an additional study or studies will be needed. Biogen and Sage are reviewing the feedback and evaluating next steps.
Christopher Viehbacher, president, and CEO at Biogen said: “The approval of Zurzuvae to treat postpartum depression is a major milestone for the hundreds of thousands of women who experience this underdiagnosed and undertreated condition.
“We appreciate the support of patients, patient advocates and researchers who helped to reach this milestone. We believe that ZURZUVAE will be an important option to treat PPD and we will thoroughly review the feedback from the FDA on the use of zuranolone in MDD to determine next steps.”
Third day reduction in symptoms
A clinical development program called Nest included two studies in adult women with PPD – called Robin and Skylark – it was these the approval of the drug was based on. They studies both met their primary endpoint - a significant mean reduction of baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, a common measure of depression severity at day 15 as compared to placebo.
In the Skylark study evaluating Zurzuvae 50 mg, all key secondary endpoints were met, with significant reduction in depressive symptoms seen as early as the third day and were sustained through to the 45th day.
The drug was generally well-tolerated with a consistent safety profile across both studies. The most common side effects were greater than or equal to 5% and greater than placebo in patients treated with 50 mg were somnolence, dizziness, diarrhea, fatigue, and urinary tract infection.
Barry Greene, chief executive officer at Sage Therapeutics, said: “Maternal mental health has been sidelined for far too long, but today’s approval of ZURZUVAE helps to change that. Women have been waiting for an oral medicine that can specifically and rapidly improve the symptoms of PPD and we are proud to be able to deliver that.
“In regard to the CRL for MDD, we are highly disappointed for patients, particularly amid the current mental health crisis and millions of people with MDD struggling to find symptom relief. We remain committed to our mission to deliver life-changing brain health medicines.”
Boxed warning
The labeling includes a boxed warning that instructs healthcare providers to advise people that Zurzuvae causes driving impairment due to central nervous system (CNS) depressant effects. People who take it should not drive a motor vehicle or engage in other potentially hazardous activities that require complete mental alertness until at least 12 hours after taking it and for the duration of the 14-day treatment course. Patients may not be able to assess their own degree of impairment.
Kristina Deligiannidis is a principal investigator in the drug’s clinical development program and professor at The Feinstein Institutes for Medical Research in Manhasset, New York.
She said: “Today marks a groundbreaking day for the treatment of PPD, as with ZURZUVAE we now have an oral treatment option that can provide rapid improvements in depressive symptoms in as early as three days for women with PPD.
“As a perinatal psychiatrist, I see the devastating impact PPD has on mothers particularly on the important mother-infant bond and long-term child development. Once available, I believe Zurzuvae will be a meaningful option for patients in need.”
According to the Centers for Disease Control and Prevention, mental health conditions are the leading cause of maternal mortality with PPD among the most common complications during and after pregnancy.
In its research the companies found the U.S., it is estimated that approximately 1 in 8 women experience symptoms of PPD. Approximately half of all PPD cases may go undiagnosed without appropriate screening. Research shows only 15.8% of women with PPD symptoms receive treatment and PPD symptoms may persist beyond the postpartum period and can lead to prolonged maternal morbidity. They also found that symptoms of PPD can include depressed mood, loss of interest in activities, changes in sleep patterns and appetite, decreased energy, feelings of guilt or worthlessness, trouble concentrating and in some cases thoughts of suicide.
Wendy Davis, executive director at Postpartum Support International, said: “Today’s approval is welcome news for the estimated 500,000 women in the United States who report experiencing symptoms of this devastating and often misunderstood illness each year.
“Women with PPD desperately need prompt care and additional treatment options that can provide quick relief so they can be healthy and present during this momentous time in their lives.”