Brexanolone, an analog of an endogenous human hormone, has been approved by the US Food and Drug Administration (FDA) for postpartum depression. Sixty-hour infusions of the drug—the first with such an indication—will cost upwards of $30,000, according to a report by the Associated Press.
In a press release, manufacturer Sage Therapeutics said it expects brexanolone, under the trade name Zulresso, to be on the market in June. Its use, on an inpatient basis, is restricted to providers in health care facilities that have been certified under an FDA Risk Evaluation and Mitigation Strategy (REMS) program. The REMS program ensures careful monitoring of patients for potential side effects such as sudden loss of consciousness and excessive sedation and with continuous use of pulse oximetry.
Approval of brexanolone was based on results of three multicenter, randomized, double-blind, parallel-group, placebo-controlled trials in women aged 18 to 45 with moderate and severe postpartum depression. Outcomes with continuous intravenous infusion for 60 hours were assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D).
Thirty clinical research centers and specialized psychiatric units in the United States were involved in two phase 3 trials. In the first study, brexanolone 90 µg/kg/ hour and 60 µg/kg/hour were tested versus placebo. In the second study, brexanolone 90 µg/kg/ hour was tested against placebo. In the first study, the lower dosage and the higher dosage of the drug were associated with 19.5-point (P= 0.0013) and 17.7-point (P=0.0252) reductions in the HAM-D score, versus a 14.0-point reduction the placebo group. The mean reduction in HAM-D scores in study two were 14.6 points for brexanolone versus 12.1 points for placebo (P= 0.0160).
According to Dr. Kimberly Yonkers, Professor of Psychiatry, of Epidemiology (Chronic Diseases) and of Obstetrics, Gynecology, and Reproductive Sciences; and Director, Center for Wellbeing of Women and Mothers at Yale School of Public Health, the difference in magnitude of effect seen in the two studiesmay have been due to the population assayed or variability in response. In both trials, the rate of response was pronounced and it was sustained for 30 days, she said, while noting that the drug is expensive and whether its benefits persist beyond 30 days is unknown.
Headache, dizziness, and somnolence were the most common treatment-emergent adverse events seen in the two studies. In the first trial, one patient treated with the 60-µg dosage had suicidal ideation and an intentional overdose attempt during follow-up. In the second trial, one patient had what were considered to be treatment-related altered state of consciousness and syncope.
Basic research leading to the development of brexanolone was done in the 1980s by scientists from the National Institute of Mental Health. They found that levels of allopregnanolone, a neuroactive metabolite of progesterone, increase during pregnancy but decrease after delivery. In some women, that postpartum drop leads to development of depression and anxiety. Brexanolone has also been studied as a treatment for a life-threatening form of epilepsy.