Sage Therapeutics has ambition to match its lofty $9 billion market valuation.
Developer of the first drug ever approved in the U.S. for postpartum depression, Sage is advancing a second-generation antidepressant it believes could treat a broader range of mood disorders that affect tens of millions of Americans.
Known as SAGE-217, the therapy also appears effective in treating postpartum depression, while a Phase 3 study testing it in major depressive disorder (MDD) is set to read out as soon as the end of this year.
Sage's plans for the drug now include developing it for treatment-resistant depression (TRD), which persists despite antidepressant use in as many as a fifth of people diagnosed with MDD.
The update from the Cambridge, Massachusetts-based biotech came during a Wednesday event billed as a "FutureCast" of Sage's R&D efforts.
Also announced were results from an open-label Phase 2 study of SAGE-217 in 35 patients with moderate-to-severe bipolar depression.
While the data suggested Sage's drug helped improve symptoms — 43% of trial participants who completed two weeks of study achieved remission — they were not as strong as some analysts had hoped for in the run-up to Wednesday's readout.
The biotech believes the development path in TRD, by contrast, to be faster and more cost-effective than in bipolar depression.
"We interpret these data as consistent with a very respectable signal suggesting a potential development opportunity in bipolar depression for SAGE-217," said Robert Lasser, Sage's head of late-stage development, during the Wednesday webcast event. "However, that potential development opportunity is balanced against the depth of other work which is still possible, we think, within MDD," he added, referring first to treatment-resistant depression but also to general anxiety disorder.
Sage's pivot is supported by a post-hoc analysis of 51 patients from a Phase 2 study of SAGE-217 in MDD and the Phase 3 trial in postpartum depression. All were unresponsive to previous antidepressant therapy.
When comparing those participants who had received the drug to those on placebo, SAGE-217 appeared to drive an improvement on a commonly used rating scale known as HAM-D.
Post-hoc analyses don't prove anything, however, and Sage will need to conduct prospective clinical testing in TRD for its new strategy to work.
TRD development offers some practical advantages, though. If the ongoing study in MDD reads out equivocal results, Sage CEO Jeff Jonas said, a TRD study could permit filing of SAGE-217 in depression when coupled with the positive trial outcome in postpartum depression.
Data in TRD could also help Sage make a better case to payers in a space with a number of widely used and now generic medications.
"We think it is the nearest term value driver and we believe that it will position SAGE-217, if and when it launches, to really be, we hope, one of the most valuable assets to be introduced in the major depression space," Jonas said on the conference call.
Sage, though, is now aiming at a therapeutic field that includes Johnson & Johnson's Spravato, or esketamine, which was approved for treatment-resistant depression in March.
Such potential competition makes the expected readout for SAGE-217 in MDD all the more important to Sage's ambitions.
Shares in the biotech have more than doubled in value since the Phase 3 success for SAGE-217 in postpartum depression, raising the company's market capitalization by roughly $5 billion. Sage is now worth more than several top biotech companies, including Ionis Pharmaceuticals, Alnylam Pharmaceuticals and Bluebird Bio.
Much of that is tied up in the potential for SAGE-217. While Sage has now launched its first drug, Zulresso, in postpartum depression, the small market for that condition and lengthy dosing regimen required has kept market expectations for future sales modest. Zulresso is given via an IV, while SAGE-217 is taken orally as a pill.
MDD, in contrast to postpartum depression, is estimated to affect 17 million Americans, three million of which are diagnosed with TRD. Success there would do much to realize Sage's research ambitions.
Sage has two other early-stage candidates which it is developing other central nervous system disorders like essential tremor and Parkinson's disease. Initial clinical data presented Wednesday support advancement into Phase 2 testing, Sage said.
Shares in Sage fell by 2.5% in Wednesday morning trading as investors reacted to the company's updates.