Sage Therapeutics Announces Brexanolone Achieves Primary Endpoints in Both Phase 3 Clinical Trials in Postpartum Depression
Statistically significant mean reduction in the HAM-D score compared to placebo at 60 hours demonstrated in both trials
Brexanolone provided a rapid and durable reduction over 30 days in depressive symptoms as measured by HAM-D in both placebo-controlled multi-center trials
Positive results support planned regulatory submissions; Company to
host conference call today at
PPD is a common biological complication of childbirth affecting a subset of women typically commencing in the third trimester of pregnancy or within four weeks after giving birth. It is estimated that PPD affects approximately 10 to 20 percent of women giving birth in the U.S. and up to half of these cases may go undiagnosed without proper screening. There are no approved therapies for PPD and there is a clear unmet medical need for treatment.
“PPD is commonly viewed as a disorder solely experienced by the mother,
but it also seriously impacts the child and family members – both
immediate and extended,” said Dr.
The Hummingbird Phase 3 program included two Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials designed to evaluate the safety and effectiveness of brexanolone in women with moderate and severe PPD. Entry criteria for participants included depressed mood and/or loss of interest and associated symptoms of depression, including appetite problems, sleep problems, motor problems, lack of concentration, loss of energy, poor self-esteem and suicidality that began no earlier than the third trimester and no later than the first four weeks following delivery.
“This is the first Phase 3 program conducted specifically in women with
PPD and these results exemplify the value of Sage’s distinct approach to
clinical research,” said
“Today illustrates what an exciting time it is in CNS research and drug
Summary of Top-line Brexanolone Phase 3 Results
Effect on Postpartum Depressive Symptoms:
In both trials at all doses, brexanolone achieved the primary
endpoint, a significant mean reduction from baseline in the HAM-D
total score at 60 hours compared to placebo.
Study 202B - Patients with severe PPD (n=122):
- Patients were randomized to one of three treatment groups (brexanolone 90 μg/kg/hour, brexanolone 60 μg/kg/hour, or placebo) on a 1:1:1 basis.
- Brexanolone 90 μg/kg/hour treatment was associated with a statistically significant mean reduction in HAM-D total score of 17.7 points from baseline compared with a 14.0 point mean reduction in HAM-D total score associated with placebo (p=0.0242).
- Brexanolone 60 μg/kg/hour treatment was associated with a statistically significant mean reduction in HAM-D total score of 19.9 points from baseline compared with a 14.0 point mean reduction in HAM-D total score associated with placebo (p=0.0011).
- Statistically significant differences in the reduction in HAM-D total score of brexanolone versus placebo were first observed at 48 hours and the effect at 60 hours was maintained through the 30-day follow-up with statistical significance for both brexanolone dose groups.
- Improvement in the Clinical Global Impression – Improvement scale (CGI-I) at 60 hours was consistent with the primary endpoint (p=0.0096 for 90 µg/kg/h dose and p=0.0124 for 60 µg/kg/h dose).
Study 202C - Patients with moderate PPD (n=104):
- Patients were randomized to one of two treatment groups (brexanolone 90 μg/kg/hour or placebo) on a 1:1 basis.
- Brexanolone treatment was associated with a statistically significant mean reduction in HAM-D total score of 14.2 points from baseline at 60 hours (p=0.0160) compared with a 12.0 point mean reduction in HAM-D total score associated with placebo.
- Statistical significance was first observed at 48 hours and remained through Day 7, but not at Day 30. However, the effect observed at 60 hours in the brexanolone group was maintained through the 30-day follow-up.
- Improvement in the Clinical Global Impression – Improvement scale (CGI-I) at 60 hours was consistent with the primary endpoint (p=0.0005).
- Study 202B - Patients with severe PPD (n=122):
Safety and Tolerability:
- Brexanolone was generally well tolerated in both studies with similar rates of adverse events across all treatment groups.
- In each trial, there was one patient who experienced a serious adverse event; neither required hospitalization and one of which was deemed by the investigator not to be study-drug related.
- The most common adverse events in the studies were headache, dizziness, and somnolence.
Detailed study results, including additional secondary endpoints, will
be submitted for presentation at an upcoming medical meeting and for
publication. Sage believes these data will be sufficient to support
submissions of regulatory applications seeking approval of brexanolone
for PPD. Sage plans to file a New Drug Application (NDA) with the
About the Hummingbird Program: 202B and 202C
The Hummingbird program included two Phase 3 multicenter, randomized,
double-blind, parallel-group, placebo-controlled trials (Study 202B and
Study 202C), designed to evaluate the safety and effectiveness of
brexanolone in women with moderate and severe postpartum depression
(PPD), aged between 18 and 45 years (inclusive) who were ≤6 months
postpartum at screening in
- Patients enrolled in both trials (202B; 202C) were required to have had a Major Depressive Episode that began no earlier than the third trimester and no later than the first four weeks following delivery, and to also be less than six months postpartum at the time of enrollment.
- Trial participants in 202B were required to have a HAM-D score of 26 or above prior to treatment. These patients were randomized to one of three treatment groups (brexanolone 90 μg/kg/hour, brexanolone 60 μg/kg/hour, or placebo) on a 1:1:1 basis.
- Trial participants in 202C were required to have a HAM-D score of between 20 and 25 prior to treatment. These patients were randomized to one of two treatment groups (brexanolone 90 μg/kg/hour or placebo) on a 1:1 basis.
For more information about these trials, please visit https://thehummingbirdstudy.com/.
Conference Call Information
Sage will host a conference call and webcast today at
About Postpartum Depression
Postpartum depression (PPD) is a distinct and readily identified major depressive disorder that is a biological complication of childbirth, affecting a subset of women typically commencing in the third trimester of pregnancy or within four weeks after giving birth. PPD may have devastating consequences for a woman and for her family, which may include significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, motor challenges, lack of concentration, loss of energy and poor self-esteem. Suicide is the leading cause of maternal death following childbirth. It is estimated that PPD affects approximately 10 to 20 percent of women giving birth in the U.S. and up to half of these cases may go undiagnosed without proper screening. There are no approved therapies for PPD and there is a high unmet medical need for improved pharmacological therapy in PPD.
About the Hamilton Rating Scale for Depression (HAM-D)
HAM-D is a validated rating scale used to provide an assessment of depression, and as a guide to evaluate recovery. This scale is an accepted regulatory endpoint for depression. The scale is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation, anxiety, weight loss, and somatic symptoms.
About Brexanolone (SAGE-547)
Brexanolone (SAGE-547) is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors. Allosteric modulation of neurotransmitter receptor activity results in varying degrees of desired activity rather than complete activation or inhibition of the receptor. Sage’s proprietary i.v. formulation of brexanolone is being developed for the treatment of postpartum depression (PPD) and has been granted Breakthrough Therapy designation by the FDA and PRIority MEdicines (PRIME) designation from the European Medicines Agency (EMA) in PPD.
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation: our
expectations regarding the potential for brexanolone in the treatment of
PPD; our view as to the unmet need for additional treatment options in
PPD and how brexanolone might address the needs of PPD patients and
families, if successfully developed and approved; our estimate as to the
number of patients with PPD; our plans and expectations with respect to
future regulatory submissions and activities related to brexanolone and
ongoing development; our views as to the potential for approval of
brexanolone and future commercialization and the impact on our company;
and our expectations regarding development, planned activities and the
potential for success of our other product candidates. These
forward-looking statements are neither promises nor guarantees of future
performance, and are subject to a variety of risks and uncertainties,
many of which are beyond our control, which could cause actual results
to differ materially from those contemplated in these forward-looking
statements, including the risks that: the clinical and non-clinical data
we have generated to date may be determined by regulatory authorities,
despite prior advice, to be insufficient to file for or gain regulatory
approval to launch and commercialize our proprietary formulation of
brexanolone and regulatory authorities may determine that additional
trials or data are necessary in order to file for or obtain approval;
regulatory authorities may find fault with the data generated at
particular clinical site or sites or with the activities of our trial
monitor or may disagree with our analyses of the results of our trials
or identify issues with our manufacturing or quality systems, and any
such findings or issues could require additional data or analyses or
changes to our systems that could delay or prevent us from gaining
approval of brexanolone; we may encounter unexpected safety or
tolerability issues with brexanolone or any of our product candidates in
ongoing or future development; the number of patients with PPD or the
unmet need for additional treatment options may be significantly smaller
than we expect; we may not be able to successfully demonstrate the
efficacy and safety of any of our other product candidates at each stage
of development; success in early stage clinical trials may not be
repeated or observed in ongoing or future studies; the efficacy data
generated in ongoing or future clinical trials may be negative or less
robust than we expect; ongoing or future clinical trials may not support
further development of our other product candidates or be sufficient to
gain regulatory approval to market any product; decisions or actions of
regulatory agencies may affect the initiation, timing, progress, number,
size and cost of clinical trials, and our ability to proceed with
further clinical trials of a product candidate in a particular
indication, or at all, or our ability to obtain marketing approval; we
may decide that a development pathway for a product candidate in one or
more indications is no longer feasible or advisable or that the unmet
need no longer exists; and we may encounter technical and other
unexpected hurdles in the development and manufacture of our product
candidates; as well as those risks more fully discussed in the section
entitled "Risk Factors" in our most recent Quarterly Report on Form
10-Q, as well as discussions of potential risks, uncertainties, and
other important factors in our subsequent filings with the