About ZULRESSO

ZULRESSO may offer rapid results
in 60 hours (2.5 days)

ZULRESSO® (brexanolone) was proven effective in the treatment of postpartum depression (PPD) in 2 Phase III clinical trials.

Phase III clinical studies of ZULRESSO showed a statistically significant reduction in PPD severity in 60 hours (2.5 days)

ZULRESSO was studied in 2 multicenter, randomized, double-blind, placebo-controlled studies in women aged 18 to 45 years with PPD who were <6 months postpartum at screening and met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for a major depressive episode with onset of symptoms in the third trimester or within 4 weeks of delivery.

Mean baseline score Mean baseline score STUDY 1 STUDY 2 SEVERE PPD(HAM-D SCORE ≥26) MODERATE PPD(HAM-D SCORE 20 TO 25) Symptom severity as measured by the HAM-D Scale Symptom severity as measured by the HAM-D Scale ≤7 ≥26 30 ≥20 ≥20 ≤7 ≥26 30 28.4 (n=41 ) † 29.0 (n=38 ) † 28.6 (n=43 ) † 22.6 (n=51 ) † 22.7 (n=53 ) † =0.025 2 ‡ P =0.001 3 ‡ P =0.016 0 ‡ P Hour 60 Hour 60 Hour 60 Hour 60 Hour 60 -17.7 -19.5 -14.0 -14.6 -12.1 ZULRESSO 90 mcg/kg/hour ZULRESSO 60 mcg/kg/hour PLACEBO Target Dosage LS mean change from baseline in HAM-D total score vs placebo 1,2 † Intention to treat population ‡ Statistically significant after multiplicity adjustments

Individual results may vary.

HAM-D=Hamilton Depression Rating Scale;
LS=least squares.

*2.5 days=Hour 60.

Patients received a 60-hour continuous intravenous (IV) infusion of ZULRESSO or placebo and were then followed for 4 weeks. Baseline oral antidepressant use was reported for 23% of patients.

  • In Study 1 and Study 2, the primary endpoint was the mean change from baseline in depressive symptoms as measured by the HAM-D total score at the end of the infusion (Hour 60)
  • In both placebo-controlled studies, titration to the recommended target dose of ZULRESSO 90 mcg/kg/hour was superior to placebo in improvement of depressive symptoms
  • In a group of 38 patients in Study 1, a ZULRESSO titration to a target dose of 60 mcg/kg/hour was superior to placebo in improvement of depressive symptoms

STUDY 11
SEVERE

Recommended target dosage:
90 mcg/kg/hour arm

Baseline: mean HAM-D score of 28.4

  • LS mean change from baseline: -17.7
  • Difference from placebo arm: -3.7 (P=0.0252)‡
  • 62.3% reduction in mean HAM-D score from baseline at Hour 60 (n=41) vs 49% with placebo (n=43, P=0.0252)

Target dosage:
60 mcg/kg/hour arm

Baseline: mean HAM-D score of 29.0

  • LS mean change from baseline: -19.5
  • Difference from placebo arm: -5.5 (P=0.0013)‡

Placebo arm

Baseline: mean HAM-D score of 28.6

  • LS mean change from baseline: -14.0

‡Intention-to-treat population.

STUDY 21
MODERATE

Recommended target dosage:
90 mcg/kg/hour arm

Baseline: mean HAM-D score of 22.6

  • LS mean change from baseline: -14.6
  • Difference from placebo arm: -2.5 (P=0.0160)‡
  • 64.6% reduction in mean HAM-D score from baseline at Hour 60 (n=51) vs 53.3% with placebo (n=53, P=0.0160)

Placebo arm

Baseline: mean HAM-D score of 22.7

  • LS mean change from baseline: -12.1

Select Important Safety Information

WARNING: EXCESSIVE SEDATION
AND SUDDEN LOSS OF CONSCIOUSNESS

Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration. Because of the risk of serious harm, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren).

Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

ZULRESSO-treated patients experienced rapid improvement of depressive symptoms vs placebo1

Change from baseline in HAM-D total score over time in Study 1 with the recommended target dosage of ZULRESSO (90 mcg/kg/hour)1,3

A similar therapeutic effect was also observed in the 60 mcg/kg/hour arm.

*2.5 days=Hour 60.

†Statistically significant after multiplicity adjustments.

‡Intention-to-treat population.

Individual results may vary.

HAM-D=Hamilton Depression Rating Scale; LS=least squares.

Durable therapeutic effect1,3

HAM-D total score did not return to baseline by Day 30 in both Study 1 and Study 2. A prespecified secondary efficacy endpoint was the mean change from baseline in HAM-D total score at Day 30.

  • In the overall Study 1 population, significantly greater reduction in HAM-D total score with ZULRESSO vs placebo was observed at Day 30 (P≤0.05)
  • In Study 1, the 60-mcg/kg/hour arm was significant at Hour-60 and maintained significance vs placebo at Day 30
  • In Study 2, the 90 mcg/kg/hour arm maintained therapeutic effect to a similar magnitude at Day 30, but did not show a greater difference vs placebo

Risk of suicidal thoughts and behaviors: ZULRESSO does not directly affect monoaminergic systems. Because of this and the comparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughts and behaviors with ZULRESSO is unknown.1

Consider changing the therapeutic regimen, including discontinuing ZULRESSO, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors.1

INDICATION

ZULRESSO® is indicated for the treatment of postpartum depression (PPD) in patients 15 years and older

ZULRESSO IMPORTANT SAFETY INFORMATION

WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS

Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.

Because of the risk of serious harm, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren).

Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

WARNINGS AND PRECAUTIONS

Excessive Sedation and Sudden Loss of Consciousness

In clinical studies in adults, 5% of ZULRESSO-treated patients compared to 0% of placebo-treated patients experienced sedation and somnolence that required dose interruption or reduction during the infusion. Loss of consciousness or altered state of consciousness was reported in 4% of ZULRESSO-treated patients compared with 0% of placebo-treated during the infusion.

In an open-label clinical study in 20 patients ages 15 to 17 years, one patient experienced dizziness and loss of consciousness.

During the infusion, monitor patients for sedative effects every 2 hours during planned, non-sleep periods. Immediately stop the infusion if there are signs or symptoms of excessive sedation. After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate. Immediately stop the infusion if pulse oximetry reveals hypoxia. After hypoxia, the infusion should not be resumed.

Concomitant use of opioids, antidepressants, or other CNS depressants such as benzodiazepines or alcohol may increase the likelihood or severity of adverse reactions related to sedation. Patients must be accompanied during interactions with their child(ren) while receiving the infusion because of the potential for excessive sedation and sudden loss of consciousness.

Patients should be cautioned against engaging in potentially hazardous activities requiring mental alertness, such as driving, after infusion until any sedative effects of ZULRESSO have dissipated.

ZULRESSO Risk Evaluation and Mitigation Strategy (REMS)

ZULRESSO is available only through a restricted program under a REMS called the ZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in serious harm.

Notable requirements of the ZULRESSO REMS include:

  • Healthcare facilities must enroll in the program and ensure that ZULRESSO is only administered to patients who are enrolled in the
    ZULRESSO REMS
  • Pharmacies must be certified with the program and must only dispense ZULRESSO to healthcare facilities who are certified in the
    ZULRESSO REMS
  • Patients must be enrolled in the ZULRESSO REMS prior to administration of ZULRESSO
  • Wholesalers and distributors must be registered with the program and must only distribute to certified healthcare facilities and pharmacies

Further information, including a list of certified healthcare facilities, is available at www.zulressorems.com or call 1-844-472-4379.

Suicidal Thoughts and Behaviors

In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that include approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD).

ZULRESSO does not directly affect monoaminergic systems. Because of this and the comparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughts and behaviors with ZULRESSO is unknown. If depression becomes worse or patients experience emergent suicidal thoughts and behaviors, consider changing the therapeutic regimen, including discontinuing ZULRESSO.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush.

Adverse reactions reported in an open-label study in patients 15 to 17 years were generally similar to those observed in clinical studies of ZULRESSO in adults with PPD.

Use in Specific Populations

  • Pregnancy: Based on findings from animal studies of other drugs that enhance GABAergic inhibition, ZULRESSO may cause fetal harm
  • Lactation: Brexanolone is transferred to breastmilk in nursing mothers. There are no data on the effects of ZULRESSO on a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZULRESSO and any potential adverse effects on the breastfed child from ZULRESSO or from the underlying maternal condition
  • Pediatric Use: The safety and effectiveness of ZULRESSO for the treatment of PPD have been established in patients 15 to 17 years. The safety and effectiveness of ZULRESSO in patients less than 15 years of age have not been established
  • Renal Impairment: No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment. Avoid use of ZULRESSO in patients with end stage renal disease (ESRD)

Controlled Substance

ZULRESSO contains brexanolone, a Schedule IV controlled substance.

To report SUSPECTED ADVERSE REACTIONS, contact Sage Therapeutics, Inc. at 1-844-4-SAGERX (1-844-472-4379) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying full Prescribing Information including Boxed Warning.

INDICATION
ZULRESSO® is indicated for the treatment of postpartum depression in patients 15 years and older.

IMPORTANT SAFETY INFORMATION
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS
Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.
Because of the risk of serious harm, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren).
Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

References

  1. ZULRESSO Prescribing Information. Cambridge, MA: Sage Therapeutics, Inc.; 6/2022.
  2. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
  3. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070.