- Sage Therapeutics will start three new clinical trials of its experimental antidepressant zuranolone in an attempt to forge a path forward for the drug after a disappointing study setback three months ago.
- That failed study, called MOUNTATIN, was intended to support an application for approval to the Food and Drug Administration. Without it, Sage has been forced to redraw its plans, leading to the update announced Wednesday.
- With the new studies, which will begin this year, Sage believes it has three routes to obtaining enough data to secure approval in either postpartum depression or major depressive disorder. Results from the studies are expected in 2021, Sage said, although turmoil from the spread of the new coronavirus could put that timeline at risk.
Sage's market value has shrunk by more than 80% since last December, when it disclosed to investors that its closely watched MOUNTAIN study fell short of its goal.
Expectations were high for zuranolone, formerly known as SAGE-217, as encouraging mid-stage data suggested it could work quicker and more safely than existing antidepressants.
But, over the course of the Phase 3 study, patients with major depressive disorder who received zuranolone appeared to do no better than those given placebo.
Such setbacks are not uncommon for psychiatric drugs, which in the past have won approval despite negative studies. Intra-Cellular's new schizophrenia treatment, for example, was cleared by the FDA in December even though one Phase 3 trial failed.
Sage's decision to start new trials means the biotech won't attempt a risky bid to win approval for the drug based on Phase 2 data and supporting trial results in postpartum depression.
Instead, the biotech will bet on three short studies to give it the additional backing it needs to convince the FDA. All three will test a two-week course of 50 mg of zuranolone, a higher dose than was used in the failed MOUNTAIN study.
Positive results for any could spring Sage to file the drug for a regulatory OK in either postpartum depression, as an acute "rapid response" treatment given alongside another antidepressant for major depressive disorder, or as an episodic therapy in MDD.
The first two paths would rely on existing data plus results from the relevant two-week study, while the third, in episodic treatment, would require data from Sage's REDWOOD study, which was paused in December following the MOUNTAIN readout.
Sage expects topline data from all three new studies in 2021, a speedy turnaround that could be ambitious as coronavirus' spread begins to put regular healthcare provision in disarray.
"Given the state of the world, there's potentially some risk to 2021 timelines (as is the case for all biotech trials), however, we note that the MOUNTAIN study only took 8 months to complete," wrote Paul Matteis, an analyst at investment bank Stifel, in a Mar. 18 note to clients.
New studies cost money, of course, and Sage said it would give updated guidance on its resource allocation in an upcoming presentation of first quarter results. The company has approximately $1 billion in cash, equivalents and marketable securities on hand, which it says will enable operations through 2022.
Keeping that runway intact, while starting new studies of zuranolone, could mean cutting back elsewhere, such as marketing for Zulresso, the company's approved intravenous postpartum depression drug. An onerous dosing regimen has kept sales slow, totaling only $4 million in 2019.
Shares in Sage fell by 5% in early morning trading, matching losses in the broader stock market.