FDA, New Products

FDA approves trailblazing postpartum depression therapy, in crucial milestone for women’s health

In a landmark decision, the US health regulator has approved the first treatment for mothers suffering from postpartum depression (PPD), a common but often overlooked and stigmatized complication of childbirth that affects an estimated 1 in 7 women.

The manufacturer of the injectable treatment — Sage Therapeutics $SAGE — has been busy, raising more than half a billion dollars through the sale of its stock to support the commercial rollout of the drug, hiring a 180-strong salesforce and setting up select centers for women to get administered with the one-time treatment under medical supervision.

The drug brexanolone — to be sold as Zulresso — was originally designed for at-home infusions. But that expectation was scuttled last year, after the agency and experts underscored concerns about fainting episodes, which occurred in 6 of 140 women exposed to brexanolone during infusion. Still, the drug won a ringing endorsement by the FDA advisory panel on the basis that designated facilities to monitor administration (encompassing a 12-hour follow-up to the 60-hour infusion) would be set up. Sage accommodated this demand by submitting a fresh risk evaluation and mitigation strategies (REMS) plan, which pushed the FDA decision date by three months to March 19.

Mike Cloonan

The treatment — which carries a boxed warning highlighting the risk of sudden loss of consciousness — is expected to launch in late June, after the DEA schedules the drug, consistent with other approved GABAergic therapies — agents that directly modulate the GABA system in the body or the brain.

Sage has assigned a list price of $7,450 per Zulresso vial, resulting in a projected average course of therapy cost of $34,000 per patient before discounts, a company spokesperson said on Tuesday.

The drug developer has been consulting with “hundreds of payers” to secure access, Sage’s chief business officer Mike Cloonan said in an interview with Endpoints News ahead of the decision.

In discussions with pharmacy benefit managers, the company feels “comfortable that we won’t have to rebate a significant portion here, because of the innovation here we’re building with Zulresso,” he said.

As part of its REMS strategy, the company is also working on establishing designated centers where women can access the therapy under medical supervision, Cloonan added, noting that “it can take months to get a site certified, registered, and to establish reimbursement pathways.”

PPD is considered a life-threatening condition because patients carry a risk of suicide, but awareness of the disorder is patchy compared to other major depressive conditions, partly due to the social stigma of being labeled an “unhappy mother” — an issue a growing number of celebrity mothers such as model and cookbook author Chrissy Teigen have brought into the cultural zeitgeist.

PPD, which is an umbrella term for several mood disorders, has profound negative effects on the maternal-infant bond and later infant development. Although a number of antidepressants exist in the market, there is little evidence of their efficacy in PPD, they usually take 6 to 8 weeks to kick in and none are specifically approved for PPD.

According to Sage, roughly 400,000 women in the United States suffer from PPD any given year, although only about half are diagnosed. With Zulresso, the company initially plans to target the severe PPD population, represented by about 20-30% of those 200,000 identified patients.

Since patients must be continuously monitored by a healthcare professional and accompanied during interactions with their children when being infused with the therapy, Stifel analyst Paul Matteis’ forecast was comparatively modest. He projected about $270 million in peak US sales in 2023, based on 10% penetration in the severe PPD setting, with no use in moderate/mild patients.

Meanwhile, the company’s keenly watched oral PPD therapy — SAGE-217 — is the one with big ticket blockbuster potential, having recently cleared a Phase III study with flying colors. The pill — also being evaluated for major depressive disorder (MDD) and other mood disorders — appears to be an improvement over brexanolone as it is not prone to inducing the loss of consciousness side effect seen with the use of the injectable. Sage intends to wait for data from a pivotal study on the pill in patients with major depressive disorder (expected in 2020) before submitting a marketing application.

Sage’s main rival is Marinus $MRNS, whose drug ganaxolone is also under evaluation for PPD. An IV formulation of ganaxolone is currently in a Phase II study in severe PPD patients, while mid-stage data from an oral formulation of ganaxolone in moderate PPD patients are expected in the first half of this year.

Zulressa’s approval bodes well for Marinus $MRNS, argued Jefferies’ Andrew Tsai in a recent note. “We think approval would have a neutral impact on Marinus, despite Sage being 2-3 years ahead, given: 1) FDA approval should de-risk the class/mechanism broadly, and 2) the FDA has required Sage to introduce a REMS program that limits its use case to a certified healthcare facility (e.g. hospital), which may open up an opportunity for Marinus. Sage‘s next-gen oral drug (SAGE-217) has also shown compelling efficacy in Phase II/III PPD and MDD studies and so far does not cause fainting (syncope) or loss of consciousness (e.g. allowing for home use), but our base case assumption is for the players to share parts of the PPD markets.”

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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