SAGE reports preliminary data from SAGE-547 Phase 1/2 clinical trial for super-refractory status epilepticus

SAGE Therapeutics (SAGE), a biopharmaceutical company developing novel medicines to treat life-threatening, rare central nervous system (CNS) disorders, today announced preliminary data from its ongoing open-label Phase 1/2 clinical trial of SAGE-547, an allosteric modulator of GABA_A receptors, in patients with super-refractory status epilepticus (SRSE). The preliminary data showed that the first three patients met both the primary endpoint, safety and tolerability, and the key secondary endpoint, efficacy, of being successfully weaned off their anesthetic agents while SAGE-547 was being administered. In particular, no drug-related serious adverse events were reported in these patients. These data were largely consistent with previously reported results of four patients with SRSE treated with SAGE-547 in emergency-use settings. Summary data were presented today at the Epilepsy Pipeline Conference in San Francisco.

"Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure and has limited treatment options," said Stephen Kanes, M.D., Ph.D., chief medical officer of SAGE Therapeutics. "These preliminary data on the potential effectiveness of SAGE-547 are very encouraging, and we look forward to obtaining the full data from this study later this year."

SAGE-547 is an allosteric modulator of both synaptic and extra-synaptic GABA_A receptors. While altering the level of synaptic GABA_A receptor activity can be beneficial in stopping seizures, this approach has limitations for the treatment of status epilepticus (SE). As SE progresses in many patients, select synaptic GABA_A receptors are down-regulated, or removed from the neuronal synaptic surface. As a result, drugs that target down-regulated receptors, such as benzodiazepines (BDZs), often are not effective in stopping SE. In pre-clinical studies, SAGE-547 has demonstrated activity in seizures that are resistant to BDZs, which may be due to its activity at extra-synaptic GABA_A receptors.