MA Startup SAGE Therapeutics' Drug For Rare Epilepsy Shows Promise In Small Study
November 10, 2014
By Riley McDermid, BioSpace.com Breaking News Staff
Sage Therapeutics said today that it has seen positive results in a Phase 1/2 clinical trial of seizure drug SAGE-547, saying it had met all primary and secondary endpoints in patients with super-refractory status epilepticus (SRSE), a critical condition in which the brain is in a state of persistent seizure.
In data from the study of 12 patients treated with SAGE-547, 73 percent of them were able to be weaned of an anesthetic agent—a crucial metric for a disease whose onset often means healthcare providers must put patients into a medically induced coma, from which they sometimes have trouble emerging.
"We believe SAGE-547 has the potential to dramatically improve the therapeutic approach for patients with SRSE, and the efficacy and safety results from this trial support our continued development of SAGE-547 as a treatment for this disorder," said Jeff Jonas, chief executive officer of SAGE.
SRSE is a life-threatening seizure condition that occurs in approximately 150,000 people each year in the U.S., of which 30,000 SE patients die.1 An SE patient is first treated with benzodiazepines, an if non-responsive, is then treated with other, second-line, anti-seizure drugs. If the seizure persists after the second-line therapy, the patient is diagnosed as having refractory SE (RSE), admitted to the intensive care unit and placed into a medically induced coma.
"We look forward to working with the U.S. Food and Drug Administration (FDA) on the appropriate design of a pivotal trial, which we anticipate initiating in the first half of 2015 pending our discussions with the FDA,” said Jonas. “We believe SAGE-547 has the potential to be the first therapy intended specifically for the treatment of SRSE, and that is very exciting for patients and clinicians managing this life-threatening disease."
The top-line data from the 12 patients, eight males and four females with a mean age of 54, found that all 12 met the primary endpoint, safety and tolerability. Of the 11 patients evaluable for efficacy, eight patients were successfully weaned off their anesthetic agents while SAGE-547 was being administered, and eight patients were successfully weaned off SAGE-547 without recurrence of SRSE. The mean duration of status epilepticus prior to treatment with SAGE-547 was 11 days.
With an overall response rate of 73 percent, SAGE-547 was generally well tolerated and no drug-related serious adverse events, as determined by the Safety Review Committee, were reported in treated patients. Mean exposure levels of SAGE-547 were approximately 200nm.
The Phase 1/2 open-label trial of SAGE-547 enrolled adult patients with SRSE who have not responded to conventional therapy with continuous intravenous antiepileptic agents and who remain in a state of persistent seizure following one or more weaning attempts from general anesthesia. In the trial, patients are administered SAGE-547 intravenously for five days while weaning from anesthesia is attempted and are monitored for four weeks following treatment with SAGE-547.
The FDA recently approved a protocol amendment for the Phase 1/2 trial submitted by SAGE that will enable the company to treat pediatric patients as young as two years old, while allowing to increase the dosage levels of SAGE-547.
"We are pleased that we were able to complete this portion of our development plan ahead of our projected timelines and would like to thank all of our investigators, patients and their families involved in this trial," said Steve Kanes, chief medical officer of SAGE, in a statement. "We are also pleased that the approved protocol amendment to our Phase 1/2 trial will enable us to explore the potential of SAGE-547 in a broader population, particularly in very young children affected with this disorder that have no other treatment options."