Sage steps up to a pivotal PhIII as brain seizure drug aces trial challenge

Sage Therapeutics has successfully wrapped a small Phase I/II study of its lead drug for rare brain seizures, coming out with a 77% response rate among evaluable patients that was a slight step up from its interim results last fall. That successful end to the study puts the biotech on the threshold of a pivotal study with a clear shot at a new drug approval that would thrust it into the commercial world.

Sage's fortunes ($SAGE) rest heavily on SAGE-547, an intravenous treatment designed to halt "super-refractory" status epilepticus (SRSE), a persistent brain seizure that often requires a medically induced coma to interrupt its course. SAGE-547 targets GABAA receptors in the brain to prevent the seizures, which the company says occurs in about 25,000 people each year.

The Cambridge, MA-based biotech recruited 25 patients for the study, basing their results on the 22 who were evaluable by the end of the trial, as opposed to intent-to-treat. Thirteen of 16 patients getting a standard dose of the drug were weaned off of anesthesia during treatment. In addition, four of the 6 patients taking a high dose were also able to get off of anesthesia. The same 77% of patients were then taken off the drug without a quick recurrence of SRSE.

The baseline for these patients was either "most extremely ill" or "severely ill" in two cases. And there were significant gains on two key measures: Global Clinical Improvement Scale and Glasgow Coma Scale.

Sage CEO Jeff Jonas

"Importantly, SAGE-547 also showed clear pharmacological activity as measured by continuous EEG in patients that had previously failed third-line treatment while burst-suppressed under general anesthesia," noted Sage CMO Stephen Kanes in a statement.

"We're very happy with the data," CEO Jeff Jonas tells FierceBiotech. He adds that the company has since nailed down 30-day follow-up results, with researchers seeing one recurrence in the first 1 to 2 weeks and three in 2 to 4 weeks.

"There's no reason why they can't be retreated," he says, adding that "in the pivotal we are offering retreatment."

None of this is likely to take Sage-watchers by surprise, as the results tend to reflect what investigators were seeing at the interim point. Now, with a successful end-of-Phase II meeting behind the company, the 30-person biotech can see how quickly they can recruit about 126 patients for Phase III and how quickly they can pull it off, aiming to be closer to a year than two years for this next big step toward launching their own U.S. commercial operations. A European partnership is under consideration, but Jonas says that Sage is ready to go it alone unless the terms are right.

A successful marketing campaign for any company aiming at an orphan market is likely to raise questions about the 6-figure drug prices that manufacturers can command for small markets. Sage isn't ready to talk dollars and cents yet, but Jonas insists that there's a reasonable price tag that can work.

"We think we can create substantial value by pricing this reasonably," says Jonas, adding that anything "exorbitant" isn't sustainable. But they'll have to work on pricing surveys with payers and users and see the final Phase III data before they can start locking in a price.

In the meantime, Jonas says that they're close to getting new data that will help determine their focus on SAGE-547 can be expanded to cover "essential tremor" and postpartum depression, which he sees as a "potentially transformative" event for the biotech. Sage is also preparing for clinical work on 689, which could be used on status epilepticus patients earlier than 547.  

Just a few weeks ago Sage--a Third Rock startup--raised $138 million in a public offering of shares. The biotech has a market cap of $1.6 billion.

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