- An experimental, fast-acting depression drug from Sage Therapeutics and partner Biogen met its main goals in a closely watched Phase 3 study that is meant to support the medicine's approval.
- Study results showed treatment with zuranolone and another approved depression drug led to a greater benefit after three days as well as, on average, over a two-week period than did a standard drug and placebo. But the drug's impact was small and waned with time, adding to questions about its prospects. Sage shares fell by as much as 19% in Wednesday morning trading.
- Sage has now completed six Phase 3 trials for zuranolone, the centerpiece of a multi-billion partnership with Biogen. Sage intends to begin submitting an approval application to U.S. regulators early this year and complete the filing before the end of 2022, CEO Barry Greene said in a statement.
Sage claims zuranolone, which is meant to act faster than standard antidepressants that can take weeks or months to work, could become an important new option for one of the most common psychiatric disorders. But the drug's development has been a roller coaster ride for the company.
In clinical practice, Sage envisions the drug being used as an acute, two-week treatment to pull people out of depression, CEO Greene said Wednesday on a conference call. Patients could get another course if they experience another depressive episode.
"We have a population of 6.8 million people per year that are just not getting a benefit from the current drugs," he said. "Having a drug that gets people better, faster is extremely valuable."
But Sage may have difficulty convincing doctors. The company redrew its clinical development plans after zuranolone failed a Phase 3 trial in late 2019. And results from several studies since then have been mixed. Treatment appears to produce an immediate effect, but one that isn't large and diminishes rapidly. An RBC Capital Markets survey of 30 psychiatrists last year also indicated concerns about the drug's side effects, mainly drowsiness and sedation.
Sage's study, titled CORAL, was meant to affirm its drug's potential as a short-course therapy that could be used on top of existing drugs. Sage randomized 425 patients and gave them a standard antidepressant alongside either zuranolone or a placebo, once nightly for two weeks. The company tweaked the study's main goal along the way, testing zuranolone's ability to reduce depressive symptoms on a widely used rating scale after three days. A secondary goal was an average of scores reported after three, eight, 12 and 15 days.
The drug succeeded on both measures, but only modestly so. In each case, the difference between zuranolone and a placebo was less than two points on the 52-point scale. Treatment was numerically superior to placebo after 15 days, but that result was not statistically significant.
The benefits diminished shortly thereafter and disappeared after 42 days. There were no new safety signals or instances of suicidal thoughts or behaviors, a key concern with other antidepressants. Drowsiness and dizziness were the most commonly reported side effects.
Sage noted the results were stronger in certain subgroups, like patients with more anxiety or higher rating scale scores at the trial's start. And because antidepressants typically start working after a few weeks and all patients knew they were on them, Sage didn't expect zuranolone to stand out after 42 days, Greene said.
"What you're seeing here is really an added placebo effect or an antidepressant effect," he added. "This drug is doing what we expect it to do."
Wall Street analysts remained skeptical. The results show Sage's drug "may be approvable and have some role in the treatment of certain depression patients," particularly those with severe symptoms and who may be at acute risk of suicide, wrote RBC analyst Brian Abrahams.
But they also show limited durability, which could curtail use of the drug to a niche market, far from the "multi-billion dollar blockbuster drug it was once hoped to be," Abrahams added in a note to clients.
The findings are "likely to debated in the physician community," added Stifel analyst Paul Matteis in a separate investor note Wednesday.