SAGE Says SAGE-547 Met Primary & Secondary Efficacy And Safety Endpoint Targets

(RTTNews) - SAGE Therapeutics (SAGE) announced that in a Phase 1/2 clinical trial of SAGE-547, an allosteric modulator of both synaptic and extra-synaptic GABAA receptors, all primary and secondary endpoint targets were achieved in patients with super-refractory status epilepticus or SRSE, a critical condition in which the brain is in a state of persistent seizure. In 73 percent of patients, treatment with SAGE-547 allowed for patients to be successfully weaned off their anesthetic agent.

Top-line data reported from 12 patients, eight males and four females with a mean age of 54, enrolled in the study show that all 12 patients met the primary endpoint, safety and tolerability. Of the 11 patients evaluable for efficacy, eight patients met the key efficacy endpoint of being 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 as an adjunctive therapy was designed to provide clear data around safety, exposure and the ability of SAGE-547 to effectively halt SRSE. The trial 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 and to increase the dose of SAGE-547 being administered to patients. SAGE said it is continuing to enroll patients as an expansion cohort in this trial, and this enrollment will proceed in parallel with SAGE's regulatory initiatives.

The company also reported that seven patients, four males and three females with a mean age of 12.5, have been treated with SAGE-547 by independent centers under emergency-use Investigational New Drug (IND) Applications. Five of these patients treated with SAGE-547 achieved resolution of SRSE either during the course of or soon after SAGE-547 treatment. The overall response rate was 71 percent, similar to the observed response rate in the Phase 1/2 clinical trial.