First Evaluation Of SAGE-547 To Treat Super-Refractory Status Epilepticus In Children Published In Annals Of Neurology

SAGE Therapeutics SAGE today announced that SAGE-547, an allosteric modulator of GABA[A] receptors, was used to treat super-refractory status epilepticus (SRSE) in two pediatric patients. The research, published online in the Annals of Neurology, is the first report of SAGE-547 treatment in children. Following treatment with SAGE-547, resolution of status epilepticus (SE) was demonstrated in both patients after weaning from general anesthetic infusions with no drug-related serious adverse effects. Both patients were treated with SAGE-547 under emergency-use Investigational New Drug Applications. "Refractory status epilepticus is a medical emergency with high risk for poor outcome. In both of these cases, the patient had been put in a medically induced coma to control seizures, and there were multiple unsuccessful attempts to wean the patient from anesthetic agents prior to treatment," said Mark Wainwright, M.D., Ph.D, director of the pediatric neurocritical care program at Northwestern University Feinberg School of Medicine and senior author of the study. "There are no truly effective treatments for refractory status epilepticus – it is incredibly exciting to work with a new therapy that may help both pediatric and adult patients affected by this disorder." The first patient, who was treated at Ann & Robert H. Lurie Children's Hospital of Chicago, was an otherwise healthy 11-year-old girl who presented with SE caused by an autoimmune disorder with antithyroid and anti-glutamic acid decarboxylase antibodies. She received an infusion of SAGE-547 over five days, after which pentobarbital sedation was weaned and discontinued. Over the remainder of the hospitalization she had intermittent, controllable seizures. She was transferred for inpatient rehabilitation, regained her ability to walk, and is now back at home, continuing to show cognitive improvement, reading, doing arithmetic and playing the piano. The second patient, a two-year-old girl, presented with SE associated with a febrile illness. SAGE-547 was infused over four days and tapered off between 96 and 120 hours. SE resolved after SAGE-547 treatment and 12 days following the completion of treatment with SAGE-547 all anti-seizure therapies were discontinued. She was transferred to inpatient rehabilitation and is now able to walk and speak. In both patients, there were no drug-related serious adverse effects detected by any of the laboratory tests used. "Mortality in refractory status epilepticus can be as high as 35 percent, and previously, pediatric patients have not participated in studies to test the effectiveness of SAGE-547," said Stephen Kanes, M.D., Ph.D., chief medical officer of SAGE and co-author of the study. "Our ongoing Phase1/2 clinical trial has yielded promising results in adult patients with super-refractory status epilepticus, and we are excited about the possibility of delivering this treatment to children, as well."