Zulresso (brexanolone) was recently approved as the first drug to treat post-partum depression (PPD). It is a medication, and naturally produced steroid that affects activity in the brain. Used by injection into a vein it involves an over 60-hour period under medical supervision. It may include considerable side effects including sleepiness, dry mouth and loss of consciousness. It is a neurosteroid and as a positive allosteric modulator of the GABA receptor. A synthetic version of a compound called allopregnanolone—it is naturally synthesized by the body from the hormone progesterone. A fast acting agent it is reported that women feel better within 48 hours after treatment and effects can last for a month.
PPD, also known as postnatal depression, can be experienced during childbirth and can impact both genders. Symptoms can include extreme sadness, low energy, anxiety and other observations associated with depression. Reports indicate it can impact the newborn child. Standard treatment includes counseling or medications. It is reported that interpersonal psychotherapy (IPT), cognitive behavioral therapy (CBT) and psychodynamic therapy are the most effective. There is tentative evidence that the use of SSRIs may provide support.
According to some sources, 15% of women experience postpartum depression around childbirth. Postpartum psychosis represents a more severe disorder and occurs in about 1 to 2 per 1000 women following childbirth. Another reference points out that postpartum psychosis occurs in about 1 in 1000 pregnancies.
The FDA’s Dr. Tiffany Farchione says “Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond. This approval marks the first time a drug has been specifically approved to treat postpartum depression, providing an important new treatment option.” Dr. Farchione continues “Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, Zulresso has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.”
Industry sponsor Sage Therapeutics plans to charge $34,000 for a treatment without insurance. Additional costs are transport and stay at the healthcare facility or infusion center. This can add up to a lot of money. More than most Americans have. Hence, our TrialSite News Price Watch article to support readers to think about creative ways toward access. Although there are about 400,000 that may experience PPD, the median annual household income is about $62,175. That’s right, for the entire household. And this is the median—half are below. Given that incidents of postpartum depression tend to be proportionally greater further down the social economic scale, Sage faces an not only an access challenge but also a revenue model question. A recent NPR article raises concerns for the Zulresso price point. Rhitu Chatterjee refers to the CDC metric that 1 in 9 women in the United States are afflicted with depression after childbirth. According to Chatterjee of NPR, “postpartum depression is more common among women from lower socio-economic groups, yet the drug, which comes with a $34,000 price tag, involves a requisite “stay in a healthcare facility”, creating a barrier for many lower-middle class to working class women. NPR notes that Dr. Maria Muzik, associate professor, department of psychiatry and obstetrics and gynecology at University of Michigan expressed “those who have the highest rates of postpartum depression and who would benefit the most, I fear it will be limited access to them.” And think of the additional barriers include “one-time continuous IV infusion over 60 hours under medical supervision at a hospital or another medical facility.”
This treatment regimen represents a considerable barrier. Many working families don’t have the luxury to just take this amount of time off. In many cases the father must be right back to work. Moreover in some cases the mother may not have a husband/partner readily available despite having a child. She may have other children and no one else to watch them. Breastfeeding represent another issue. Although it wasn’t allowed during the trial the study revealed little risk—but is it fully conclusive? And then there is, of course, the $34,000 price tag in a country with a mean annual household income at $62,175.
Sage’s CEO Jeff Jonas was quoted in a Bloomberg Business Week article written by Cynthia Koons that “every physician and every institution will make a choice” noting “is it better to help someone get better in two and a half days or send them home?” Not so easy, claims Ritu Baral, a biotech analyst with Cowan Inc., who professes “the only moms who can really afford to take it are the ones who can arrange for 60-plus hours of childcare” and Baral continued “it’s not easy for probably two-thirds of people.” Again back to data mentioned previously—that postpartum depression could be correlated to socioeconomic status—in the lower tiers. Put another way, there are more women struggling with PPD also struggling economically than those women privileged to exist in high income households.
In the build up to the approval, Sage readied a commercial strategy, undoubtedly understanding many of these challenges. To the biotech ventures’ credit, they sought to consider a holistic range of options advancing development of a family-centric site of care strategy with potential options (premised on acceptance by FDA that these approaches can fit in the REMS category) including:
- In-patient hospital setting
- Supervised home care
- Alternate sites of care
Sage pursued a partnership with Lash Group, a part of AmerisourceBergen, “to establish a robust patient support model leveraging innovative technologies coupled with Sage-led case management support for postpartum patients” in addition to the final completion of a National Patient Support Center based in Raleigh, North Carolina. Additionally Sage is in the middle of a full court press with Payers—evangelizing of the benefits and the importance of coverage. Moreover, they presented a comprehensive set of reports on the humanistic burden of postpartum depression at a recent Payers’ conference. To get a better grasp of people’s daily challenges, Sage partnered with PatientsLikeMe patient network. Sage reported they were “working with a top U.S. health economist” to demonstrate value.
Sage reports in their latest 10K that sales will initially target women with more severe symptoms of postpartum depression. The FDA’s REMS requirement confines them to only certain situations; plus the 60 hours and ancillary costs of transport, hotel, etc. narrow the available patient pool. Based on their forecast, out of 400,000 women in the U.S. that are diagnosed with symptoms, about 50% are formally diagnosed. That frankly, narrows the population down to 200,000 and we estimate of the 20% of that 200,000 or 40,000 only about 15% of that number will represent very extreme cases that many payers may cover—equaling 6,000 patients per year. Factoring in socioeconomic elements as well as uncertainty about payer commitment we estimate about only about 2,500 to 5,000 women may be able to take advantage of this powerful new treatment—cetaris paribus. Analysts probably concur. The Raymond James investment bank, as noted in BioPharmadive indicated that the price is probably too high—estimating ultimate market adjusted net price of Zulresso around $14,000. Perhaps payers will cover for only the most severe cases. The social determinants of health impact American healthcare in a big way.
Amy Brown and Edwin Elmhirst of Evaluate looked at the potential revenue spread for Zulresso. They noted that threating its broader adoption are the cost and access issues TrialSite News raises herein—and tagging them as associated with social determinants of health. Moreover, potential oral competition from Sage’s own SAGE-217 and Marinus’s ganaxolone could further box in Zulresso as a niche treatment for extreme cases. There are essentially three revenue scenarios including the (1) conservative (2) intermediary and (3) home run.
- Conservative equals up to $100 million in sales
- Intermediary equals $100 to $250 million in sales
- Home run equals $500+ million
At the established target price to reach $100 million there would need to be 2,941 patients in a year. Based on metrics identified earlier, severe postpartum depression postpartum psychosis represents about 1 to 2 out of every 1,000 births. Sage Therapeutics near $8 billion market capitalization is based, to some extent, on the success of Zulresso—its launch is an indicator of vision, strategy and execution and fosters more market confidence for the bigger potential blockbuster SAGE-217. Presently, Sage generates approximately $90 million in revenue on EBITDA losses of $392 million as reported by Yahoo Finance. They do keep $922 million cash in bank—and it will be needed. Drug development is very expensive. Commercialization may be four-times as costly. Sage is to be commended-we believe that they are an innovative company producing high quality, novel treatments. But they are not a big pharma with lots of extra money. Establishing the conditions for market acceptance of Zulresso will represent a more expense proposition than they may have anticipated. To open up more demand will probably require a lower price tag. Sage’s longer term valuation rests on a number of other factors—many promising for them as the more broad-based CNS depression markets, for example, are far bigger and more access points.
Sage Therapeutics has delivered a powerful new drug to the market. It is the first drug approved by the FDA specifically for postpartum depression. Based on clinical trials the treatment, although cumbersome to deliver—involving intravenous injection and a 60 hour stay at the hospital—has been approved by the FDA and declared safe and effective. This can make a difference not only to a mom’s health but a child’s long term well-being and vitality not to mention the whole family unit. Severe PPD can lead to tragic consequences. From one vantage, Sage has delivered a breakthrough drug—without question. But Sage must think differently and consider the social determinants of health and “the whole person.” This includes not only their immediate health issues, but also their economic and social milieu, and other societal factors and forces influencing the patient and their situation. We noted that the median American household income is just under $65,000. PPD is experienced at high levels amongst lower socio-economic demographic segments One research paper referenced earlier concludes “financial hardship and unwanted pregnancy are associated with antenatal and postpartum depressive symptoms. Women with a history of depression and those with poor pregnancy outcomes are especially vulnerable to depressive symptoms during the childbearing year.”
At a price tag of $34,000 (not to mention the hospital stay and other direct and indirect costs), unless Payors are 100% all-in and industry sponsor include comprehensive supports for seamless care coordination, the cost and access challenges become well beyond most mothers (and family) ability to participate. Perhaps Payers will recognize this and provide the required subsidies in combination with Sage integrated care coordination and subsidy programs to help overcome such barriers.
Sage clearly is looking into supportive infrastructure to help make the treatment process easier and more convenient. Moreover, they will canvass payers and physicians to evangelize for the benefits. But healthcare in America is really costly; and concierge service typically costs even more–well beyond what most Americans can come near to affording. Time represents another material element. For those with the economic means, time is more available. For those that struggle to make ends-meet, it is not. 60 hours is a big deal for family units that are below the median household income levels. There may be a smaller subset of Zulresso patients than Sage initially planned for that can benefit from the treatment unless some of these social determinant barriers are overcome.
Mr. O’Connor has spent nearly 20 years providing technology and value-added services to the clinical trials and health technology industry. An entrepreneur, he has been instrumental in building different ventures focusing on FDA 21 Part 11 enterprise document management, technology-enabled patient recruitment services, clinical safety data exchange, as well as population health and community care coordination for at-risk populations with Eccovia Solutions. He is a co-founder of a public benefit corporation launching a global clinical research site accreditation standard–ACRES ReServ. At TrialSite News Mr. O’Connor and team have developed a comprehensive clinical research site data base and intelligent clinical news curation engine to contribute to clinical research transparency with a focus on sites and investigators. He earned his combined MA and JD from the University of California (Los Angeles and Hastings College of the Law) and undergraduate from San Francisco State University.