FDA Approves Cambridge Company's Groundbreaking Drug For Postpartum Depression

(CNN) -- For the first time in history, the US Food and Drug Administration has approved a drug specifically indicated for the treatment of postpartum depression, which experts say offers new hope to women and physicians.

On Tuesday, the FDA announced the approval of an intravenous infusion of the drug brexanolone, which will be sold as Zulresso. It has been shown in clinical trials to work within hours to treat the symptoms of postpartum depression, a serious mental illness that impacts 1 in 9 new mothers after childbirth.

"Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond. This approval marks the first time a drug has been specifically approved to treat postpartum depression, providing an important new treatment option," Dr. Tiffany Farchione, acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, said in a press announcement on Tuesday.

"Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, Zulresso has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient," she said.

The treatment is administered as a single 60-hour IV drip and was found to have mild side effects, such as headache, dizziness or excessive sleepiness, but also sudden loss of consciousness. Yet some women may face barriers accessing this type of treatment, as it requires 60 hours of time. The drug will likely be priced around $20,000 to $35,000 per treatment, Sage Therapeutics, the company that developed the drug, confirmed.

The initial list price for Zulresso in the United States will be $7,450 per vial, resulting in a projected average course of therapy cost of $34,000 per patient before discounts, according to the company. The actual number of vials used before discounts can vary from patient to patient.

The medication will be available in June, said Dr. Jeff Jonas, CEO of the Cambridge-based biopharmaceutical company that developed the drug. The drug will be available only through a restricted program called the Zulresso Risk Evaluation and Mitigation Strategy (REMS) Program that requires the drug be administered by a health care provider in a certified health care facility, the FDA said in a news release announcing the approval.

"There are no FDA approved antidepressants for postpartum depression, so approval of the first medication of its kind is a breakthrough for patients," said Dr. Kristina Deligiannidis, the director of Women's Behavioral Health at Northwell Health's Zucker Hillside Hospital in New York, who was involved in two of the drug's clinical trials as a researcher.

Without any treatment, postpartum depression can last for months or even years, according to the National Institute of Mental Health. Studies showed the brexanolone was effective regardless of when postpartum depression symptoms began.

In the United States, it's estimated that every year, more than 400,000 infants are born to mothers who are depressed. Treatment options for postpartum depression have included counseling or therapy with a mental health professional and antidepressant medications, but no antidepressant medication has been specifically FDA-approved to treat postpartum depression. Also, antidepressant medications generally don't provide an immediate relief of symptoms and may take several weeks to help.

"Brexanolone in phase II and III trials demonstrated rapid antidepressant effects," said Deligiannidis, who is also an associate professor at the Feinstein Institute for Medical Research and member of the Anxiety and Depression Association of America.

Those effects are something that Stephanie Hathaway, a Connecticut-based mother of two, knows well.

A 'breakthrough' drug gets tested

When Hathaway brought her first baby home from the hospital, she was just as excited and nervous as most new moms -- but she also experienced crying spells and troubling thoughts that she couldn't shake.

"The first two weeks I was crying excessively," Hathaway said. At first, her husband and she thought her tears were from "the baby blues," a feeling of sadness or emptiness after giving birth that goes away within a few days.

"But after that I had intrusive thoughts," she said. "Those were, 'Your daughter deserves a better mom,' and 'Your husband deserves a better wife.' "

Then Hathaway knew she needed help when one day she was holding her daughter and she feared what she might do to herself once she put her baby down.

That year, in 2014, Hathaway was diagnosed with postpartum depression and was treated with traditional antidepressant medications, which she said helped "over time."

A few years later, in 2017, Hathaway had a second child, and was prescribed the same antidepressants during that pregnancy -- but the medications were not helpful in relieving her symptoms.

A friend told Hathaway about clinical trials being conducted to evaluate the effectiveness of brexanolone in treating postpartum depression. Hathaway enrolled in a trial.

"It was a 60-hour infusion and in the first 12 to 18 hours I felt the biggest difference," Hathaway said.

"Those intrusive thoughts that played on repeat in my head, those went away and didn't come back," she said, adding that as a side effect, "I just had one very small instance of standing up and feeling lightheaded."

In 2016, the FDA granted brexanolone a "breakthrough therapy designation" for the treatment of postpartum depression. Such a designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.

Results from two phase III trials of brexanolone, conducted across 30 clinical research centers and specialized psychiatric units in the United States, published in the journal The Lancet in August.

The trials, conducted in 2016 and 2017, involved more than 200 women who had symptoms of postpartum depression, which were assessed by standardized research scales. The women were followed up with over 30 days. Sage Therapeutics funded the research.

In those studies, some of the women were given 60-hour IV infusions of smaller or larger doses of brexanolone while others were given a placebo. The researchers found that the women who received brexanolone infusions had "significant and clinically meaningful" reductions in their depression scores.

In the first study, by the end of 60 hours, the average reduction was 19.5 points in the brexanolone group that received smaller doses, and 17.7 points in the brexanolone group that received larger doses, compared with 14 points in the placebo group.

In the second study, which had only one brexanolone group, the average reduction in score was by 14.6 points in the brexanolone group compared with 12.1 points in the placebo group at 60 hours, the researchers found.

Overall, at 60 hours, about 75% of women who received brexanolone were at least 50% improved in their symptoms and about half of women who received brexanolone were no longer clinically depressed, Deligiannidis said.

Among the patients who had a response at 60 hours, 94% did not relapse at the 30-day followup.

The most common side effects included headache among 15.7% of patients; dizziness among 13.6%; and somnolence or excessive sleepiness among 10.7%, the researchers found.

The researchers wrote in the study that their findings "provide strong evidence for the efficacy and safety of brexanolone injection in women with moderate to severe post-partum depression."

Limitations of the studies include that the women were followed only for 30 days, so the duration of treatment effects beyond that were not included in the data.

The treatment also requires 60 hours of an IV -- which, for women without support at home or living in poverty, could be difficult. Low-income mothers are at high risk for postpartum depression. The treatment also could interrupt breastfeeding, and patients are encouraged to discuss the risks and benefits of breastfeeding with their physician.

Additionally in the trials, brexanolone had the most robust effects on women experiencing severe postpartum depression whereas results were more modest among others whose postpartum depression was less severe.

'It potentially sets a new standard for treatment'

"What has been consistent is that brexanolone had a very robust response -- and what's been most exciting to me, in terms of participating in this new drug development, was the rapid onset of response. The drug works quickly," said Dr. Samantha Meltzer-Brody, a professor of mood and anxiety disorders at the University of North Carolina School of Medicine in Chapel Hill, who was a researcher in those phase III trials for the drug.

"My greatest hope is that this increases awareness. What's heartbreaking is the number of women who suffer in silence and do not get the treatment that they need," she said. "People need to reach out and get screened and get treatment, regardless of if treatment is with brexanolone or not."

The clinical data supporting the effectiveness of brexanolone in helping women recover from postpartum depression sheds new light on the neurobiology of the illness, as well as depression during other life periods, said Catherine Monk, professor of medical psychology in obstetrics and gynecology and psychiatry at Columbia University Irving Medical Center and director of research in the women's program in psychiatry at NewYork-Presbyterian/Columbia University Irving Medical Center in New York. Monk was not involved in the drug trials.

Monk, who is also a research scientist at the New York State Psychiatric Institute, added that "because its effects are truly expedited, within days, it potentially sets a new standard for treatment for severe postpartum depression."

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