Sage Therapeutics’ Postpartum Depression Drug Heads to the FDA

SAGE Therapeutics, located in Cambridge, Massachusetts, has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for brexanolone (SAGE-547) to treat postpartum depression (PPD).

Brexanolone is an allosteric modulator of synaptic and extrasynaptic GABAA receptors. It is dosed in an intravenous (IV) formulation. It was granted Breakthrough Therapy Designation by the FDA and PRIority Medicines (PRIME) designation by the European Medicines Agency (EMA).

The application is based on data from the Hummingbird Program, which included three multicenter placebo-controlled clinical trials. Each one studied the safety and effectiveness of the drug in women with moderate or severe PPD between the ages of 18 and 45 years who were six months or less postpartum in the U.S.

PPD affects 10 to 20 percent of women who give birth each year in the U.S. In November, the drug had positive results in two Phase III trials, showing significant ability to decrease patients’ depression symptoms compared to placebo.

Xconomy notes, "Still, whether the drug—which requires a 60-hour IV infusion—will succeed commercially is an open question. In a recent research note, for instance, RBC Capital Markets’ Brian Abrahams wrote that it ‘will be critical for the drug’s adoption’ for home infusions to be available, rather than hospital IV infusions."

The company is studying a pill formulation, SAGE-217, in PPD that works similarly to brexanolone, but it hasn’t proven if it works as effectively as the IV formulation. A Phase II trial is ongoing, with results planned for later this year.

Sage is also evaluating SAGE-217 in major depressive disorder (MDD), where it has also received Breakthrough Therapy designation based on a Phase II trial. It expects to launch additional trials of the drug in MDD this year. The company also expects to begin clinical development of SAGE-217 in bipolar depression, Parkinson’s disease and insomnia sometime this year. The company also has SAGE-324, which is presently in IND-enabling studies and is being studied for indications involving GABA hypofunction, such as essential tremor and epileptiform disorders. It plans to initiate a Phase I trial of the drug in the first half of this year.

Sage is also developing SAGE-718 and SAGE-904 for neurological disorders, and expects to begin Phase I trials for SAGE-718 in the first half of this year. SAGE-904 is currently in IND-enabling studies.

At its fourth-quarter and year-end financial report on February 22, 2018, the company noted it had $518.8 million in cash, cash equivalents, and marketable securities, and another $631.1 million it had raised in February 2018 from an underwritten public offering. Its R&D expenses were $50.9 million for the quarter, which for the year-end were $210.3 million.

"By thinking differently about CNS, Sage has accelerated innovation across the development cycle, from discovery through development, and is now progressing toward potential commercial operations and patient care," said Jeff Jonas, Sage’s chief executive officer, in a statement at the time. "While our 2017 achievements demonstrate the strength of our R&D organization, successful execution against our 2018 goals will drive our planned transition to a commercial company with the opportunity to create a new standard of care for women with postpartum depression. In addition, our broad portfolio of fully-owned, internally developed molecules creates further opportunity to transform the lives of patients with life-altering CNS disorders and the potential to drive near and long-term value."

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