SAGE Announces Initiation of Phase 1 and First Dosing of SAGE-217

Sage Therapeutics

today announced it has initiated dosing in a Phase 1 single ascending dose trial evaluating SAGE-217 in healthy volunteers. Initial top-line results from the study are expected in the first half of 2016. "Administering the first dose of SAGE-217 is another significant milestone for SAGE's R&D organization," said Albert Robichaud, Ph.D., Chief Scientific Officer of SAGE. "SAGE-217 is a novel GABAA modulator, selected for its high potency and potential to be developed for once- daily oral administration, and is a good example of our leading drug discovery capabilities. We plan to continue our focus on pipeline expansion with next generation GABA and NMDA product candidates for CNS disorders." SAGE-217 is a next generation positive allosteric modulator that has been optimized for greater selectivity of GABAA receptors and a pharmacokinetic profile intended to support once-daily oral dosing. SAGE is developing SAGE-217 for high frequency seizures associated with select neurological disorders, including orphan epilepsies, and other GABAA dysfunction-related disorders, such as essential tremor. In preclinical development, SAGE-217 demonstrated anti-seizure and anxiolytic activity in multiple animal models, including potent activity in seizure models such as Dravet and Fragile X syndromes. James Doherty, Senior Vice President of Research at SAGE, said, "With SAGE-217, our preclinical testing revealed robust and dose-related activity, a wide therapeutic index and good oral bioavailability across a broad range of animal models. SAGE-217 also exhibited high selectivity for synaptic and extrasynpatic GABAA receptors with very limited secondary pharmacology and few off-target effects in animals, making it a desirable candidate for clinical development. This suggests that, if SAGE-217 successfully completes Phase 1, it has the potential to be studied across several orphan epilepsies characterized by high seizure burden, as well as in other disorders, such as essential tremor and postpartum depression, where GABAA dysfunction may play a role." The Phase 1 single ascending dose study of SAGE-217 is a double-blind, placebo-controlled trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of SAGE-217 administered orally in approximately 80 healthy adult volunteers.