The drug's sponsor filed for FDA approval earlier this week under breakthrough therapy status.
Less than a week after filing with FDA, Sage Therapeutics came to the annual gathering of obstetricians to present phase 3 results for its breakthrough therapy, which could be the first drug specifically approved to treat postpartum depression (PPD).
Results for brexanolone IV were presented in poster sessions Friday and Saturday at the 2018 Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists (ACOG), being held April 27-30, 2018, in Austin, Texas. Three years ago, ACOG updated its guidelines to call on obstetricians to screen perinatal patients at least once for depression and be prepared to treat patients if they met criteria for depression, or refer them to behavioral health specialists who could treat them.
Brexanolone IV requires a 60-hour infusion. A Sage Therapeutics representative said while the infusion required patients to be in a clinical setting for the phase 3 trials, the company is studying other delivery models. The infusion required breast feeding to be interrupted for 7 days. (A pill form is also being developed.)
In the 2 sets of results, women with either moderate or severe PPD were evaluated on the 17-point Hamilton Rating Scale for Depression (HAM-D), a physician-administered scale used to evaluate a patient’s depression level before, during, and after treatment. Patients were also evaluated with the Edinburgh Postnatal Depression Scale, a patient self-assessment commonly used in clinical practice, to compare treatment and placebo groups. Patients were then randomized based on the protocol of the separate studies.
Results for Severe PPD
In the study for women with severe PPD, 120 women with a HAM-D score of ≥26 were randomized 1:1:1 to receive an infusion of placebo, brexanolone 60 µg/kg/h, or brexanolone 90 µg/kg/h. Results presented Friday showed the average reduction in the HAM-D score from baseline for the 90 μg dose was 17.7 points. The average reduction for the 60 µg dose was 19.9 points from baseline, and the average reduction with placebo was 14.0 points from baseline.1
Brexanolone began working quickly: statistically significant reductions in the HAM-D scores were seen at 48 hours and the effects at 60 hours were sustained at 30 days; by contrast, most anti-depressants take up to 2 weeks to work, which can present problems for mothers experiencing fatigue, insomnia, and issues bonding with their newborn.
The average age for women in the placebo group was 27.0 years; the average age for the 60 90 µg group was 27.3 years, and the average age for the 90 µg group was 27.8 years. In the placebo group, a slightly larger share (30.4%) had PPD onset during the third trimester, compared with 23.4% and 22.2% in the treatment groups. The rest had PPD onset within 4 weeks of delivery.
Both studies were funded by Sage Therapeutics.
Results for Moderate PPD
In the study for women with moderate PPD, 108 women with a HAM-D score of 20-25 were randomized 1:1 to receive an infusion of placebo or brexanolone 90 µg/kg/h. In this study, the data for the treatment group showed the average reduction in HAM-D from baseline appeared to be 15.0 at 60 hours, compared with 12.0 for placebo.2
The ages of the participants were similar to those in the severe PPD study: an average or 27.4 years in the placebo group and 28.4 years in the treatment group; 22.2% in both the placebo and treatment groups had PPD onset in the third trimester with the rest during the first 4 weeks after delivery.
For both studies, a Clinical Global Impression Improvement scale taken at 60 hours found results consistent with the HAM-D scores. Brexanolone was well-tolerated, and only 3 adverse events (AEs) leading to discontinuation were reported across both studies. The AEs reported by 5 or more people in either study were headache, nausea, dizziness, and infusion site pain.
Brexanolone is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors, proteins that were identified as possible treatment targets a decade ago in experiments with mice. These preclinical experiments showed that the GABAA fell during pregnancy to keep the body in sync with neurosteroid levels, and then rose after birth. But if dysregulation occurs, depression results.