Date: 2014-09-02
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the Twelfth Eilat Conference on New Anti-Epileptic Drugs in Madrid, Spain
Company: Sage Therapeutics (USA - MA)
Product: SAGE-217
Action
mechanism: SAGE-217 is a GABA-potentiating, second-generation neuroactive steroid that has demonstrated favorable CNS exposure (rodent brain to plasma ratio >1.3-3.2), an attractive pharmacokinetic profile and the potential for IV, IM and oral administration. This neuroactive steroid acts as a positive allosteric modulator of synaptic and extra-synaptic GABAA receptor subtypes. Unlike many of the naturally occurring neuroactive steroids, SAGE-217 has a pharmacokinetic profile to potentially support once-daily oral dosing and a selectivity profile that minimizes potential off-target side effects. SAGE-217 is currently in preclinical development for a range of seizure conditions, including orphan genetic epilepsy disorders, such as Rett syndrome and Dravet syndrome.
Disease: seizure conditions, including orphan genetic epilepsy disorders, such as Rett syndrome and Dravet syndrome
Therapeutic area: CNS diseases - Genetic diseases - Neurological diseases - Rare diseases
Country:
Trial details:
Latest
news: * On September 2, 2014, SAGE Therapeutics presented preclinical data on its second-generation neuroactive steroid, SAGE-217, at the Twelfth Eilat Conference on New Anti-Epileptic Drugs in Madrid, Spain. The data suggest improved activity for this compound versus other first-generation neuroactive steroids in development, as well as favorable selectivity and pharmacokinetic profile of the drug. Preclinical data generated through in vitro electrophysiology studies utilizing mammalian cell lines showed that SAGE-217 was more efficacious in in vitro assays of GABAA modulation than either allopregnanolone or ganaxolone at both synaptic α1β2γ2-containing GABAA receptors and extra-synaptic α4β3δ-containing GABAA receptors. SAGE-217 also exhibited reduced off-target activities compared to the known first-generation analogs. In addition, in comparison to first-generation neurosteroids, SAGE-217 demonstrated efficacy at reduced levels of plasma and brain exposure in models of benzodiazepine-resistant seizure.
The company also presented data previously reported on SAGE-547, an allosteric modulator of GABAA receptors currently in clinical development for super-refractory status epilepticus (SRSE). “The data presented suggest the potential for high potency and selectivity of SAGE-217 and its potential efficacy in well-validated, preclinical seizure models. This promising compound is the second of several we plan to develop in our seizure franchise targeting a range of disorders from status epilepticus to orphan genetic epilepsies, such as Dravet syndrome”said Albert Robichaud, Ph.D., chief scientific officer of SAGE Therapeutics.
