The FDA has approved Sage Therapeutics’ treatment for postpartum depression, Zulresso (brexanolone).
Zulresso is the first product specifically indicated for postpartum depression PPD, which can start during pregnancy or any time up to a year after the baby’s birth, and affects an estimated 400,000 women in the US each year.
In severe cases it can raise the risk of suicide or even harm to the baby, but until now no treatment has been specifically licensed for the condition.
“Today’s approval of Zulresso represents a game-changing approach to treating PPD,” said Dr. Samantha Meltzer Brody, director of the Perinatal Psychiatry Program, UNC Center for Women’s Mood Disorders and primary investigator of the Zulresso clinical trials.
Brody says the ability to rapidly reduce symptoms in the disorder was an “exciting milestone in women’s mental health.”
Unlike conventional antidepressants, which can take weeks to kick in, the single infusion starts working within 2-3 days of dosing and can lift women quickly out of the sadness, anxiety, irritability, and social withdrawal that can accompany PPD.
The approval also represents the first product on the market for Sage Therapeutics. The Boston, Mass-based company was first established in 2010, but saw earlier lead candidates fall by the wayside before Zulresso emerged.
Analysts predict Zulresso could eventually achieve annual revenues around $250m, based on its US list price of $34,000 per treatment.
This will be limited by a number of factors. Zulresso has an unusually long 60-hour intravenous infusion period, and this will require a hospital stay.
While the drug has been shown to take effect rapidly, trials also suggested that its benefits also tailed off quickly once treatment is discontinued.
Awareness raising is a key issue for PPD, as an estimated half of all PPD cases may go undiagnosed. This factor, along with the need for a hospital stay – and potentially some separation from their newborn child – means treatment is likely to be restricted to the more severe cases.
Sage Therapeutics’ Jeff Jonas
“We are proud to be a part of this important moment in mental health, creating the opportunity for an unprecedented change in the way postpartum depression is thought about and treated moving forward,” said Jeff Jonas, M.D., chief executive officer of Sage.
The FDA approval of Zulresso is based on clinical trials in women with moderate and severe PPD, aged between 18 and 45 years who were 6 months or more postpartum at screening, and who had onset of symptoms no earlier than the third trimester and no later than the first four weeks following delivery.
Zulresso achieved its primary endpoint at all doses, a significant mean reduction from baseline in the Hamilton Rating Scale for Depression (HAM-D) total score, a common measure of depression severity, at 60 hours compared to placebo. A reduction of depressive symptoms was also seen as early as 24 hours, and the treatment effect was maintained through the 30-day follow-up.
The most common adverse events in the studies were sleepiness, dry mouth, loss of consciousness and flushing.
Investors see the greatest potential in Sage’s pipeline, most especially SAGE-217, which has a similar mechanism to Zulresso, but which has a much more convenient daily oral formulation.
Analysts forecast sales in excess of $1bn for the compound if it can gain approval in PPD and in the larger patient group suffering from major depressive disorder (MDD) with a phase 3 trial in the this latter group already underway.
The company recently raised $575m to fund its pipeline, including other assets such as lead neurology candidate SAG-324 for essential tremor and epileptiform disorders, and neuropsychiatry candidate SAGE-718 for cognition-related disorders such as Huntington’s disease, both of which are in phase 1 testing.