The therapy’s New Drug Application was accepted and granted Priority Review in May of this year, after having been granted Breakthrough Therapy designation in September 2016.
Samantha Meltzer-Brody, MD
Novel injection therapy brexanolone has been proven to be a potentially rapid and durable treatment of post-partum depression (PPD) in new mothers, according to the results of a pair of phase 3 trials.
In recent analysis led by Samantha Meltzer-Brody, MD, of the Department of Psychiatry at University of North Carolina School of Medicine Chapel Hill, and funded by Sage Therapeutics—owner of the fast-track designated intravenous therapy—brexanolone showed significant benefits for patients with moderate to severe post-partum depression versus placebo.
The new findings give credence to Sage’s submission for marketing approval with the US Food and Drug Administration (FDA). The therapy’s New Drug Application was accepted and granted Priority Review in May of this year, after having been granted Breakthrough Therapy designation in September 2016.
To assess the efficacy and safety of positive GABAA receptor modulator brexanolone, investigators conducted 2 double-blind, randomized, placebo-controlled studies at 30 clinical research centers and specialized psychiatric clinics in the US. Qualified patients were aged 18-45 years old, having been 6 months post partum or less at the time of screening, with PPD and a qualifying Hamilton Rating Scale for Depression (HAM-D) score of at least 26 for the first study, and 20-25 for the second.
The scale is a 17-item test to assess for depression, with greater numbers indicating greater severity. Investigators excluded women with renal failure that required dialysis, anemia, allergies to allopregnanolone or progesterone, or a medical history of schizophrenia, bipolar disorder, or schizoaffective disorder.
Across both studies, 375 women were randomized 1:1:1 to receive either single intravenous injection brexanolone 90 mcg/kg per h (BRX90) or 60 mcg/kg per h (BRX60), or matching placebo for 60 h. Investigators assessed for a primary efficacy endpoint of change from baseline in patient HAM-D total score at 60 h.
In study 1, 138 patients were randomly assigned to BRX90 (n = 45), BRXO60 (47), or placebo (46). At 60 h, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19.5 (SE 1.2) in patients administered BRX60 and 17.7 (SE 1.1) in patients administered BRX90. Patients administered placebo reported a mean point reduction of just 14.0, indicating a score difference of -5.5 (95% CI; -8.8 to -2.2 [P = .0013]) and -2.5 (95% CI; -4.5 to -0.5 [P = .0160]), respectively.
In the second study, 25 patients in the BRX90 group had reported adverse events (AEs), versus 24 patients treated with placebo. The most commonly reported AEs related to the treatment were headache, dizziness, and somnolence. Across both studies, 2 patients treated with brexanolone (one for each dose) reported a pair of serious AEs, though just 1 was treatment-emergent (altered state of consciousness, syncope).
Meltzer-Brody noted the therapy’s model for treating depression is novel from any previously-approved drug. If approved by the FDA later this year, brexanolone will not only be the first drug specifically indicated for PPD, but the first drug to deviate from the selective serotonin reuptake inhibitor (SSRI) anti-depressant standard of treatment speed.
“Having a drug approved to treat PPD that works quickly and effectively, yet is also durable, would be a huge step forward for psychiatry in general,” Meltzer-Brody said in a statement.
The study, "Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials," was published online in The Lancet.