SAGE has built a robust product pipeline initially focused on acute and orphan CNS indications with clinically validated targets and accelerated development timelines – enabling us to bring important medicines to patients rapidly.
Status Epilepticus (SE) is an acute, life-threatening form of epilepsy or seizures that occurs in approximately 150,000 U.S. patients each year, with a mortality rate of nearly 20%. Refractory SE, in which currently available treatment options are not effective, occurs in the approximately one-third of SE patients. These patients are moved to an ICU setting with little or no treatment options.
SAGE has developed SAGE-547, a potent positive allosteric modulator (PAM) of both synaptic and extra-synaptic GABAA receptors that rapidly advanced into Phase 1/2 clinical development for the orphan indication of refractory SE in early 2014. SAGE-547 demonstrated robust findings in preclinical models of SE, including significantly increased efficacy over current standard-of-care benzodiazepine treatment, and compelling early human experience data.
SAGE is also currently developing a seizure franchise of advanced next generation compounds of novel GABAA PAMs for the treatment of SE and other forms of seizure and epilepsy.
The need for safe and effective anesthesia products is growing significantly with more than 80 million general anesthesia procedures annually in the U.S. and EU and more than 50 million procedural sedations per year. There is a significant demand for innovative anesthesia products that can improve quality and safety while reducing the cost of anesthesia care. With the number of outpatient procedures increasing, a procedural sedation product with an enhanced safety profile that does not require administration by an anesthesiologist could make a dramatic impact on this market.
SAGE has advanced several novel chemical entities that have demonstrated similar time to sedation and recovery, as well as a dramatically improved therapeutic index in preclinical models when compared to the existing standard therapy, propofol. Propofol is widely used but can pose significant risks for respiratory and cardiac depression, can cause pain upon injection, and has been associated with both bacterial contamination and shortages due to its formulation. The SAGE drig discovery effort has identified SGE-689 as an IV anesthetic for procedural sedation that is designed to offer increased efficacy and safety over propofol. The SGE-689 program is moving toward a Phase 1 clinical trial in 2014.
SAGE is continuing to build its robust pipeline of proprietary positive and negative allosteric modulators targeting NMDA receptors at a unique, previously unknown binding site (non-glycine site). By targeting NMDA receptors at a novel allosteric binding site, SAGE is able to mitigate the issues typically seen with alternate approaches including limited efficacy, tolerance, and safety. SAGE is evaluating future programs in cognition (schizophrenia, Alzheimer’s disease, Parkinson’s disease, and other conditions), autism, depression, epilepsy, and pain.