Brexanolone effective for moderate, severe postpartum depression

Sage Therapeutics recently announced phase 3 findings that indicated efficacy and safety of brexanolone, formerly known as SAGE-547, for postpartum depression.

“[Postpartum depression (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,” study researcher Samantha Meltzer-Brody, MD, MPH, of the University of North Carolina at Chapel Hill School of Medicine, said in a press release. “Symptoms of PPD should not be overlooked by new moms or those in their support networks and the health care community should encourage discussion and appropriate action. These data meaningfully advance our understanding of PPD and may prompt medical professionals to evaluate how PPD is perceived, identified and treated within their practices in the future. In these studies, brexanolone provided a profound and durable effect over the study period that could be an important step in potentially changing the way health care providers think about treating this disorder.”

To assess safety and efficacy of brexanolone for PPD, researchers developed the Hummingbird program, which consisted of two phase 3 multicenter, randomized, double-blind, parallel-group, placebo-controlled trials among women aged 18 to 45 years with moderate and severe PPD. Study participants experienced a major depressive episode no earlier than the third trimester and no later than the first 4 weeks following delivery.

Study 202B

In study 202B, participants had Hamilton Rating Scale for Depression (HAM-D) scores of 26 or higher prior to treatment. Participants were randomly assigned to receive 90 g/kg of brexanolone per hour; 60 g/kg of brexanolone per hour; or placebo.

From baseline, women who received 90 g/kg of brexanolone exhibited a statistically significant mean reduction in HAM-D total scores of 17.7 points, compared with a 14-point reduction in the placebo group.

Women who received 60 g/kg of brexanolone had a mean reduction in HAM-D scores of 19.9 points from baseline.

Statistically significant differences in HAM-D total score reductions between brexanolone and placebo were first observed at 48 hours and the effect at 60 hours was maintained through a 30-day follow-up with statistical significance for both brexanolone dosages.

At 60 hours, women who received 90 g/kg of brexanolone and 60 g/kg of brexanolone exhibited significant improvement in Clinical Global Impression-Improvement (CGI-I) scores, consistent with the primary study endpoint.

Study 202C

In study 202C, participants had HAM-D scores between 20 and 25 prior to treatment. Women were randomly assigned to receive 90 g/kg of brexanolone per hour or placebo.

From baseline to 60 hours, participants who received 90 g/kg of brexanolone exhibited a mean reduction in HAM-D total score of 14.2 points, compared with a 12-point reduction among those who received placebo.

Researchers first observed statistical significance at 48 hours, which remained through day 7 but not at day 30. However, effect observed at 60 hours among the brexanolone group was maintained through the 30-day follow-up.

Improvement in CGI-I at 60 hours was significant and consistent with the primary study endpoint, according to researchers.

Safety

Brexanolone was generally well-tolerated in both studies with comparable rates of adverse events among all treatment groups.

The most common adverse events included headache, dizziness and somnolence.

“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,” Jeff Jonas, MD, CEO of Sage, said in the release. “We are pleased with the findings, specifically the rapid onset of action and duration of effect observed in all arms of the Hummingbird program. We believe the data represent an unprecedented opportunity in the development of treatments for PPD, and may serve as the catalyst for a paradigm shift in how the disease is approached and, if approved, may change how PPD is treated.”

Sage Therapeutics recently announced phase 3 findings that indicated efficacy and safety of brexanolone, formerly known as SAGE-547, for postpartum depression.

“[Postpartum depression (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,” study researcher Samantha Meltzer-Brody, MD, MPH, of the University of North Carolina at Chapel Hill School of Medicine, said in a press release. “Symptoms of PPD should not be overlooked by new moms or those in their support networks and the health care community should encourage discussion and appropriate action. These data meaningfully advance our understanding of PPD and may prompt medical professionals to evaluate how PPD is perceived, identified and treated within their practices in the future. In these studies, brexanolone provided a profound and durable effect over the study period that could be an important step in potentially changing the way health care providers think about treating this disorder.”

To assess safety and efficacy of brexanolone for PPD, researchers developed the Hummingbird program, which consisted of two phase 3 multicenter, randomized, double-blind, parallel-group, placebo-controlled trials among women aged 18 to 45 years with moderate and severe PPD. Study participants experienced a major depressive episode no earlier than the third trimester and no later than the first 4 weeks following delivery.

Study 202B

In study 202B, participants had Hamilton Rating Scale for Depression (HAM-D) scores of 26 or higher prior to treatment. Participants were randomly assigned to receive 90 g/kg of brexanolone per hour; 60 g/kg of brexanolone per hour; or placebo.

From baseline, women who received 90 g/kg of brexanolone exhibited a statistically significant mean reduction in HAM-D total scores of 17.7 points, compared with a 14-point reduction in the placebo group.

Women who received 60 g/kg of brexanolone had a mean reduction in HAM-D scores of 19.9 points from baseline.

Statistically significant differences in HAM-D total score reductions between brexanolone and placebo were first observed at 48 hours and the effect at 60 hours was maintained through a 30-day follow-up with statistical significance for both brexanolone dosages.

At 60 hours, women who received 90 g/kg of brexanolone and 60 g/kg of brexanolone exhibited significant improvement in Clinical Global Impression-Improvement (CGI-I) scores, consistent with the primary study endpoint.

Study 202C

In study 202C, participants had HAM-D scores between 20 and 25 prior to treatment. Women were randomly assigned to receive 90 g/kg of brexanolone per hour or placebo.

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From baseline to 60 hours, participants who received 90 g/kg of brexanolone exhibited a mean reduction in HAM-D total score of 14.2 points, compared with a 12-point reduction among those who received placebo.

Researchers first observed statistical significance at 48 hours, which remained through day 7 but not at day 30. However, effect observed at 60 hours among the brexanolone group was maintained through the 30-day follow-up.

Improvement in CGI-I at 60 hours was significant and consistent with the primary study endpoint, according to researchers.

Safety

Brexanolone was generally well-tolerated in both studies with comparable rates of adverse events among all treatment groups.

The most common adverse events included headache, dizziness and somnolence.

“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,” Jeff Jonas, MD, CEO of Sage, said in the release. “We are pleased with the findings, specifically the rapid onset of action and duration of effect observed in all arms of the Hummingbird program. We believe the data represent an unprecedented opportunity in the development of treatments for PPD, and may serve as the catalyst for a paradigm shift in how the disease is approached and, if approved, may change how PPD is treated.”