Sage Therapeutics this morning reported that its most advanced clinical prospect, a neurological drug known as brexanolone, failed its first big test.
Sage (NASDAQ: SAGE), of Cambridge MA, said the drug didn’t do much better than a placebo in a Phase 3 trial of patients with a rare, life-threatening form of epilepsy called super refractory status epilepticus (SRSE).
There are no FDA approved therapies for SRSE; patients have continuous seizures despite anti-epileptic drugs, have to be placed into a medically induced coma to stop them, and can’t be safely woken up by other treatments. Brexanolone’s main goal in the Phase 3 study was to help these people wake up, and get at least a chance to resume their lives.
Sage said Tuesday, however, that brexanolone didn’t fare much better than a placebo at helping wean patients in its trial off of anesthetics, and stay off of them without suffering another seizure for at least 24 hours. In the study, 43.9 percent of patients on brexanlone were successfully weaned off other drugs, compared to 42.4 percent of those on placebo. Those results weren’t statistically significant.
Sage said the rates of serious side effects and death were similar between those on drug or placebo, but didn’t provide details. It will present more information at a future medical meeting. The company, however, will no longer develop the drug for SRSE. Shares of Sage fell more than 25 percent, to $66.25 apiece, in pre-market trading Tuesday morning.
The news marks setback for Sage, which went public in 2014 at $18 per share, raising $138 million off of early data from this trial. The company had seen its value rise nearly five fold—shares closed at $88.52 apiece on Monday. But since the IPO, Sage has used the cash it’s been able to raise to broaden both the program and its pipeline, giving brexanolone another, much more potentially lucrative chance to succeed and putting other drugs into clinical testing as well. As Sage has been developing brexanolone it has run small studies in other diseases to see if the drug might produce a signal. One of those small trials, in postpartum depression (PPD), was positive, giving Sage at least the opportunity to come up with a therapy for a condition that affects an estimated 600,000 women in the U.S. every year, according to the Centers for Disease Control and Prevention. Given today’s failure, the stakes are now even more significant for Sage when it produces data from these trials later this year.
“This was in many ways our smallest opportunity,” CEO Jeff Jonas said of SRSE, on a conference call with analysts Tuesday morning.
Jonas asserted that brexanolone’s failure in SRSE wasn’t a harbinger of similar problems in the PPD trials, citing differences in the diseases themselves, the variability in the underlying cause that led to patients’ SRSE, and the “consistency of data” the drug has generated so far in PPD. Brexanolone, for example, succeeded in a placebo-controlled Phase 2 trial in PPD, whereas it hadn’t previously conducted that type of study in SRSE. Even so, given today’s setback, is he now worried the drug isn’t doing what it is meant to do—dial down the inhibitory neurotransmitter known as GABA?
“Absolutely not,” Jonas said on the conference call. “This was an extremely complex disorder, multiple underlying conditions. We’re very confident with the science.”
Phase 3 trials in psychiatric disorders are notoriously difficult, often bedeviled by a higher than expected placebo effect and other problems. Still, analysts Tuesday morning distanced Sage’s failure in SRSE from its potential in other diseases. “We still think PPD—-and by extension major depressive disorder….should stand on its own merits,” wrote Leerink Partners analyst Paul Matteis.