Following the news that the FDA granted approval for Sage Therapeutics and Biogen’s novel antidepressant Zurzuvae (zuranolone) for the treatment of postpartum depression (PPD) but rejected the drug for the treatment of major depressive disorder (MDD), issuing a complete response letter (CRL);

Philippa Salter, Senior Neurology Analyst at GlobalData, offers her view:

“Zurzuvae is a significant breakthrough for treating PPD. It is the first oral medication approved for the indication, and as such is significantly more convenient for patients compared with Sage Therapeutics’ previously approved drug for PPD, Zulresso (brexanolone). Zulresso has seen poor uptake since its FDA approval in 2019 due to its time-consuming intravenous infusion route of administration, which takes 60 hours, and the requirement for continuous monitoring due to the risk of excessive sedation or sudden loss of consciousness during administration. In contrast, Zurzuvae only carries a warning that the drug may cause driving impairments for up to 12 hours. However, the FDA did note that the drug has potential for abuse and so will undergo a scheduling review before it can enter the market.

“Another strength of Zurzuvae compared to the common off-label therapies for PPD such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors is its novel mechanism of action, which means it has a rapid onset of action, with reduction in depressive symptoms seen as early as three days after beginning medication compared to three to six weeks. Additionally, as an acute therapy, administered for just two weeks, Zurzuvae will be particularly attractive for patients who do not want to be locked into taking long-term maintenance therapy, especially mothers who may be concerned about any medication they take entering their breast milk.

“Although the approval for PPD is significant, receiving a CRL for MDD is very disappointing for Sage Therapeutics and Biogen, given the large patient population with MDD versus PPD and thus significant missed commercial potential. Furthermore, Zurzuvae had been well poised to target a key unmet need consistently highlighted by key opinion leaders interviewed by GlobalData: for pharmacotherapies that can demonstrate rapid antidepressant effects in patients with MDD. However, the FDA requires a further clinical trial to confirm the efficacy of Zurzuvae for MDD, with Sage Therapeutics and Biogen yet to confirm whether they will move forward.

“An unsure future for Zurzuvae in MDD is advantageous for Axsome Therapeutics’ Auvelity (bupropion + dextromethorphan), giving the product longer to fully establish itself on the market as the first oral, fast-acting antidepressant for MDD, having been approved by the FDA in August 2022. GlobalData forecasts strong global (8MM: US, France, Germany, Italy, Spain, UK, Japan, and Canada) sales of $1.3 billion by 2029 for Auvelity.”