Sage_Logo_RGBSage Therapeutics isn’t the company its founders originally intended.

Third Rock Ventures started Sage in 2011 to develop drugs for big neurological disorders such as schizophrenia and traumatic brain injury. Along the way, however, the Cambridge, MA-based company decided to focus on rare neurological disorders that could be moved quickly through the clinic.

That switch is proving prescient so far: Sage got the full top-line data from its first clinical trial today, and the results are promising.

Sage (NASDAQ: SAGE) reports that SAGE-547, its lead drug, met all primary and secondary goals in a small, 12-patient clinical trial for super-refractory status epilepticus (SRSE), a rare, life-threatening form of epilepsy characterized by continuous or repeating seizures. Patients with the condition are put into anesthesia-induced comas to suppress their seizures when antiepileptic drugs fail. There are no approved therapies for SRSE.

So far, SAGE-547 has proven to be to be safe and allowed clinicians to wean eight of the patients in the small Phase 1/2 trial off those anesthetics, effectively halting their disease. A 12th patient in the study could not be evaluated, so the drug essentially worked in eight of 11 patients, or 73 percent. Sage CEO Jeffrey Jonas (pictured above) says the 12th patient was diagnosed with status epilepticus after taking a lethal overdose of drugs in a suicide attempt; that patient died from the toxins he ingested, not from anything related to SAGE-547.

Jonas says that the company had been looking for a response rate of at least 50 percent: “Even at a 50 percent response rate we think it [would be] very exciting for patients where there are no approved therapies for a condition that’s often life-threatening,” he says. “We’re obviously delighted with the data.”

Sage will now have to recreate these small-sample size results in a larger, longer trial. It hopes to talk to the FDA about starting a pivotal study—the last required before regulatory approval—in the first half of 2015. The company has already been cleared to treat patients as young as two years old by expanding enrollment in the current study, in which the average patient age was 54.

Those patients—eight males and four females— had SRSE for an average of 11 days. In that time, they hadn’t responded to intravenous antiepileptic drugs and couldn’t be taken off anesthesia without suffering continuous seizures. Jonas says the trial was designed to reflect real-world usage. The company enrolled patients with a range of potential underlying conditions, ages, and reasons for developing status epilepticus—be it stroke, cancer, a drug overdose, existing epilepsy, or something else—who were in intensive care and needed interventional treatment to stop their seizures.

They were each given an IV dose of SAGE-547 for five days while being weaned off of the anesthetics, then were monitored for four weeks.

Sage’s main goal was to show the drug was safe, and it says that there were no drug-related serious adverse events in the 12 patients in the trial (it hasn’t yet disclosed data about lesser side effects). Sage also hit a secondary mark to show the drug worked, too. What that means, in a practical sense, is that patients could be taken out of their comas without immediately seizing up. Jonas adds that Sage is seeing this happen regardless of patients’ ages or the cause of their conditions.

“That’s one of the encouraging things,” he says. “These patients may be treated with a myriad of underlying agents, and despite that, the drug has been very well tolerated.”

Separately, five of seven patients who have been permitted to take SAGE-547 under compassionate use (71 percent) were free of SRSE either “during the course or soon after…treatment,” according to a statement from the company. Those data don’t count towards Sage’s trial, but at minimum the data back up the type of response Sage is seeing in its study.

Jonas says Sage will start testing SAGE-547 at higher doses and in longer durations as it expands its current trial, to see the reactions of those who don’t respond to the drug at a lower dose. A pivotal study might require anywhere from 100 to 200 patients, and the main goal would likely be to enable a SRSE patient to wake from his or her coma and stay seizure-free for a certain period of time.

“That’s probably the most clinically relevant endpoint that will drive the use of the drug and will add value to patients’ lives, so that’s probably what we’ll shoot for,” Jonas says. “Happily, if you look at the data that we have so far, the patients meet those endpoints anyway.”

Status epilepticus affects about 150,000 people each year in the U.S. Roughly 25,000 of those patients, Jonas says, are “super refractory,” meaning that they don’t respond to treatment with benzodiazepines (now-generic drugs that have been around for decades) or other anti-seizure drugs, and they can’t be taken out of induced comas without suffering seizures.

SAGE-547 is an allosteric receptor modulator, designed to create equilibrium among the neurotransmitters in the brain and calm the overexcitement of brain signals that are thought to lead to disorders such as status epilepticus. ’547 is supposed to do so for SRSE patients by dialing down the inhibitory transmitter known as GABA.

Well after it launched in 2011 with a $35 million Series A round from Third Rock, Sage shifted its strategy from bigger central nervous system diseases to rare ones, in part due to a fortuitous case of a University of California, Davis doctor who used its experimental drug as a last resort for a status epilepticus patient.

Switching its focus to the rare status epilepticus has paid dividends. All within the space of a few months earlier this year, the FDA granted SAGE-547 a fast-track designation and orphan drug status, and investors carried Sage to a $90 million IPO. At the time, Sage had shown that four SRSE patients dosed with SAGE-547 in the Phase 1/2 study all responded to its drug.