Zuranolone is a huge triumph for PPD—but it could negatively impact women’s health research
In August 2023, the FDA approved the first-ever pill to treat postpartum depression (PPD). Getting FDA approval for any drug sounds like a miracle to me, someone who works in late-stage clinical research. Day-to-day, I live the grind and rollercoaster of what it takes to bring a drug to market. On average, it’s an investment upwards of $1 billion per drug and over a decade of development and clinical testing. Zuranolone, to be marketed as Zurzuvae by Sage Therapeutics, otherwise known as the PPD pill, addresses a condition affecting 10% to 15% of new moms. This is a big win for new parents. How investors reacted, however, creates reluctance to fund future women’s health initiatives.
How zuranolone works
First, let’s understand the impressive promise of this new drug. Prior to zuranolone, clinicians have prescribed selective serotonin reuptake inhibitors (SSRIs) off-label for PPD. Compared to SSRIs, this newly approved drug works faster and with fewer doses than existing treatments. SSRIs typically take 4 to 6 weeks to demonstrate improvement in mothers’ symptoms. Zuranolone is only a 2-week daily oral dose.
Furthermore, trial participants reported improvements in just three days of use. The mechanism of intervention is different: SSRIs work by increasing levels of serotonin in the brain. Zuranolone is a synthetic hormone replacement of allopregnanolone that helps calm down stress responses. As allopregnanolone production is associated with progesterone, the dramatic drop of progesterone post delivery leads to a correlating drop in allopregnanolone.
Zuranolone can offer relief by addressing this known hormone imbalance. For so many people affected by postpartum depression, this new drug is hope. Its specific intended use, or indication, for PPD could also reduce stigma and increase willingness to take the drug.
Women’s health solutions are perpetually underfunded
What ensued, however, brings concerning implications. Within a week of the FDA’s approval for zuranolone for PPD, Sage Therapeutics’ stock price was absolutely decimated, dropping by more than half in value. The flip side of the FDA’s approval of zuranolone for PPD was the denial of the drug’s use for clinical depression, also called major depressive disorder (MDD).
Without FDA approval for this broader indication, the drug cannot be explicitly marketed to clinicians and consumers to treat clinical depression. The estimated sales of zuranolone for the PPD market is estimated at $250 million to $500 million in annual sales. However, the potential to market it for the broader indication was valued at over $1 billion. Investors acted quickly on this news, devaluing Sage Therapeutics.
Despite its landmark achievement in women’s health, Sage Therapeutics announced job cuts to minimize impacts to its bottom line and assuage investors. What should have been a celebratory week became one of trepidation.
This fallout has two implications for new moms and women. The most direct is zuranolone’s price point. The cost of the drug has not yet been determined. However, with a narrower indication, negotiations with pharmacy benefits managers (PBMs)—intermediaries that essentially determine cost to patients—will look different. The resulting decisions will affect how and whether insurance companies cover the drug, ultimately impacting affordability and access.
Beyond affordability, this incident perpetuates underfunding of women’s health in clinical innovation, venture capital, and private equity. Sage has been effectively punished for its successes. This loss may deter other companies from investing in women’s health.
Other companies will evaluate Sage’s fall as a precedent warning, heeding that the market size for the women’s health segment is “too small” for real profit. Clinical research is notoriously skewed towards treating white males. As a result, the ensuing FDA-approved drugs are not representative of the issues impacting the general population. When it is primarily men in the room making decisions, opportunities to improve breast pump technology or solve polycystic ovary syndrome (PCOS) are deprioritized.
Those who control the dollars struggle to empathize with our key issues. Zuranolone’s story means this segment will continue to be trivialized and dismissed with suboptimal treatments.
Keeping our promise to innovation
This event hits home for me on many levels. It is a fascinating interplay of two distinct professional experiences in clinical research and finance, but also a delicate connection to my own personal journey. I can still feel the trench of suffering I fell into during the postpartum experience. It is a shadow that haunts the joys of motherhood I feel today.
I remember the helplessness and remorse that people said time would eventually fix.
I remember scoffing at the PPD screening questionnaires I took. The “right” answers that allowed me to stay in self-denial were so obvious.
To me, admitting this internal struggle felt like admitting I was unfit for motherhood.
With zuranolone marketed for PPD, I see a promise of better screening and openness to treatment. By identifying the physiological basis of PPD, we can reduce the stigma around mental health, measuring the imbalance of hormones just as we identify breaks in bones.
I hope that this latest is a dismissible setback for investments in women’s health and not the ensuing narrative. We need to design business cases around women, full stop. For my own daughter, I hope for a more equitable, inclusive and compassionate healthcare system.
