Postpartum depression is one of the most common psychological conditions after childbirth, affecting roughly one in eight new mothers.
“Postpartum depression is one of the most common — often underdiagnosed complications of childbirth,” said Dr. Samantha E. Meltzer-Brody, director of the University of North Carolina Center for Women’s Mood Disorders. The pandemic has likely only made the situation worse.
Sage Therapeutics (Nasdaq:SAGE) and Biogen (Nasdaq:BIIB) are optimistic about the prospects of zuranolone, a drug candidate for postpartum depression, that met primary and key secondary endpoints in the Phase 3 SKYLARK study. If approved, the drug would be the first oral therapy for postpartum depression.
The treatment response in the placebo-controlled study was “robust,” Meltzer-Brody said.
Patients who received a 50 mg daily dose of zuranolone, a neuroactive steroid, had a 15.6 reduction in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) scale on Day 15.
“When you see that kind of dramatic fall in HAM-D, you’re looking at the difference between someone who’s really struggling and having very significant symptoms that impair their ability to function versus someone that has resolution of most symptoms,” Meltzer-Brody said.
The drug could give psychiatrists a new fast-acting oral tool for treating postpartum depression. “The response rates are high, and it’s well-tolerated,” Meltzer-Brody said. Zuranolone could be “a really important step forward for the field,” she added
Dr. Meltzer-Brody was a principal investigator for novel clinical trials for the now FDA-approved Zulresso (brexanolone) from Sage Therapeutics, an IV-based fast-acting treatment for postpartum depression.
While zuranolone has the advantage of being an oral drug, it is unlikely to replace brexanolone, which is also a neuroactive steroid, Meltzer-Brody said. There is a continued need for IV-based antibiotics even though oral antibiotics are much more convenient for most patients. With brexanolone, response rates can often be seen at the 24-hour mark, Meltzer-Brody explained.
In the SKYLARK study, zuranolone recipients saw an average 9.5 point drop in HAM-D score at Day 3. After reaching a 15.6 point reduction at Day 15, drug recipients saw their HAM-D scores continue to improve, falling 16.3 points by Day 28 and 17.9 points by Day 45.
SKYLARK is the seventh and last completed Phase 3 study of zuranolone. The studies found that the drug candidate safely reduced depression symptoms in as few as three days for patients with postpartum depression and major depressive disorder.
More data are needed to understand the durability of the therapeutic effect. “Right now, we know the durability of the length of time of the clinical trial,” Meltzer-Brody said.
Clinical investigators had similar questions related to brexanolone, which showed a sustained response for up to 30 days following infusion. “Our group published a paper this past year looking at following people out for a variable length of time after people had finished [brexanolone therapy], and we saw durability of response for many people, Meltzer-Brody said.
Earlier this year, Sage and Biogen began the rolling submission of an NDA to the FDA for zuranolone to treat major depressive disorder. The companies plan to submit an associated NDA filing for postpartum depression in the first half of 2023.
If FDA approved, zuranolone could be an important treatment option for new mothers who may have a significant symptom burden associated with postpartum depression. As the doctor taking care of these patients, you want to do nothing more than intervene quickly,” Meltzer-Brody said.
In terms of drug therapy options for postpartum depression, selective serotonin reuptake inhibitors (SSRIs) have been the most commonly prescribed antidepressant. “Certainly, SSRIs can be effective in some women,” Meltzer-Brody said. “But they can take quite a bit of time to work.” It can take at least four to six weeks before women see relief. In some cases, it can be a matter of months before physician can determine an effective dose of an SSRI. “And the number of women that get benefit [from SSRIs] is smaller than we would like.”
The FDA approval of brexanolone in 2019 provides effective therapy for severe postpartum depression, but it is a continuous IV infusion over a total of 60 hours. “It has its place, but for more widespread use, an oral drug would certainly be preferred,” Meltzer-Brody said. “And, a medication that’s going to work quickly really just becomes so enormously important and the ability to reduce suffering.”
Meltzer-Brody acknowledged that many psychiatrists have reservations about new drugs. “It takes some time for any new kid on the block to have more widespread acceptance, but I think drugs that are well tolerated and efficacious quickly make their mark,” she concluded.
Filed Under: clinical trials, Drug Discovery, Obstetrics & gynecology, Psychiatric/psychotropic drugs, Uncategorized