Approval based on results from three pivotal trials showing treatment with ZULRESSO provided significant and rapid reduction of depressive symptoms within days
Postpartum depression is the most common medical complication of childbirth, estimated to affect approximately 400,000 women annually in the U.S.
Sage Therapeutics, a biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, announced that the U.S. Food and Drug Administration (FDA) has approved ZULRESSOTM (brexanolone) injection for the treatment of postpartum depression (PPD). ZULRESSO is the first and only medicine specifically approved to treat PPD, the most common medical complication of childbirth. ZULRESSO is expected to be available in late June following scheduling by the U.S. Drug Enforcement Administration, which is expected to occur within 90 days.
PPD can affect women during pregnancy or after childbirth. It is estimated PPD affects approximately one in nine women who have given birth in the U.S. Symptoms may include sadness, anxiety, irritability, withdrawing from friends or family, having trouble bonding with her baby and thinking about harming herself or more rarely, her baby. Without proper screening, up to half of PPD cases may go undiagnosed.
ZULRESSO was evaluated by the FDA under Priority Review, which is reserved for investigational therapies that, if approved, may offer significant improvements in the treatment, prevention or diagnosis of a serious condition. In 2016, ZULRESSO was also granted Breakthrough Therapy Designation status, underscoring the significant unmet need in women with PPD.
The FDA approval of ZULRESSO is based on findings from three multicenter, randomized, double-blind, parallel-group, placebo-controlled trials, designed to evaluate the safety and effectiveness of ZULRESSO in women with moderate and severe PPD, aged between 18 and 45 years who were ≤6 months postpartum at screening and who had onset of symptoms no earlier than the third trimester and no later than the first four weeks following delivery.
In all trials at all doses, ZULRESSO achieved the primary endpoint, a significant mean reduction from baseline in the Hamilton Rating Scale for Depression (HAM-D) total score, a common measure of depression severity, at 60 hours compared to placebo. A reduction of depressive symptoms was also seen as early as 24 hours, and ZULRESSO maintained effect through the 30-day follow-up. The most common adverse events in the studies were sleepiness, dry mouth, loss of consciousness and flushing.
Ligand Pharmaceuticals Inc. stands to collect a $3 million milestone payment plus 3 percent royalties on sales after FDA score with Zulresso (brexanolone) in postpartum depression (PPD). The drug, a formulation of allopregnanolone, a potent, positive, allosteric modulator of synaptic and extrasynaptic GABA type A receptors, uses Captisol, Ligand’s cyclodextrin platform, to improve solubility, stability and bioavailability. Sage gains a first-to-market advantage with Zulresso, but the clearance should lift hopes for the likes of Marinus Pharmaceuticals Inc., developing GABAA modulator ganaxolone in PPD. Zulresso’s go-ahead came with an also-expected risk evaluation and mitigation strategies (REMS) program, which Sage negotiated with U.S. regulators during a PDUFA date delay. The REMS arrangement calls for a health care provider to administer the drug in a certified facility, providing Zulresso as a continuous I.V. infusion over a period of two and a half days with constant monitoring for oversedation. Sage priced the boxed-warning drug, first ever approved for PPD, at $34,000 per course of treatment.