CAMBRIDGE, Mass., Aug. 6, 2015 (GLOBE NEWSWIRE) -- SAGE Therapeutics (NASDAQ:SAGE) today announced it has reached agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the STATUS Trial (SAGE-547 Treatment as Adjunctive Therapy Utilized in Status Epilepticus), a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial to evaluate SAGE-547 as a treatment for patients with super-refractory status epilepticus (SRSE). The SPA provides agreement from the FDA that the Phase 3 STATUS Trial can adequately address objectives in support of a U.S. regulatory submission for approval of SAGE-547 for the treatment of patients with SRSE. SRSE is a rare, life-threatening condition of persistent, unremitting seizure, for which there are no approved therapies.
"This is a major accomplishment for SAGE Therapeutics. By obtaining FDA agreement on the Phase 3 STATUS Trial design, endpoints, patient population and statistical approach, we have a clear path on moving forward with our development and regulatory plan for SAGE-547 in SRSE. As first movers in seeking a treatment for this life-threatening disorder, we believe our SPA is an important mechanism to further de-risk our development pathway. We look forward to enrolling patients in the Phase 3 STATUS Trial imminently," said Jeff Jonas, M.D., chief executive officer of SAGE Therapeutics.
The STATUS Trial is designed to assess the efficacy and safety of SAGE-547 in approximately 126 patients with SRSE, aged two years or older, and will be conducted in the U.S., Canada and Europe. Patients will be randomized 1:1 to receive either SAGE-547 or placebo in addition to standard-of-care third-line anti-seizure agents for six days. The planned primary endpoint of the Phase 3 clinical trial will be successful resolution of status epilepticus (SE) after weaning the patient off all third-line agents, and SAGE-547 or placebo, without resumption of SE within 24 hours after completion of blinded SAGE-547 or placebo administration.
SAGE's Phase 3 open-label expanded access protocol, designated Study 302, was initiated in April 2015 and continues its enrollment. Study 302 is designed to make SAGE-547 available to patients in the U.S. who are affected by SRSE and who have not been admitted to, nor can be transferred to, a planned STATUS Trial clinical site.
In a completed Phase 1/2 open-label clinical trial, SAGE-547 demonstrated robust activity, with a 77 percent response rate in 22 evaluable patients with SRSE, and also a favorable tolerability profile. Independent of treatment response, six patient deaths occurred within the trial period, all driven by underlying conditions. Although 64 percent of patients reported serious adverse events, none were drug-related as determined by the Safety Review Committee.
About Special Protocol Assessments
The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application.
Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 clinical program. The SPA agreement may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety. For more information on Special Protocol Assessment, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080571.pdf.
SAGE-547 is an allosteric modulator of both synaptic and extra-synaptic GABAA receptors. SAGE-547 is an intravenous agent in Phase 3 clinical development as an adjunctive therapy for the treatment of super-refractory status epilepticus (SRSE). SAGE-547 has been granted both Fast Track and orphan drug designations by the U.S. Food and Drug Administration (FDA) for the treatment of SRSE. The active pharmaceutical ingredient has been contributed under agreement by the Regents of the University of California and the University of California, Davis.
About Status Epilepticus
Status epilepticus (SE) is a life-threatening seizure condition that occurs in approximately 150,000 people each year in the U.S., of which 30,000 SE patients die.1 An SE patient is first treated with benzodiazepines, and if no response, is then treated with other, second-line, anti-seizure drugs. If the seizure persists after the second-line therapy, the patient is diagnosed as having refractory SE (RSE), admitted to the ICU and placed into a medically induced coma.
Currently, there are no therapies that have been specifically approved for RSE; however, physicians typically use anesthetic agents to induce the coma and stop the seizure immediately. After a period of 24 hours, an attempt is made to wean the patient from the anesthetic agents to evaluate whether or not the seizure condition has resolved. Unfortunately, not all patients respond to weaning attempts, in which case the patient must be maintained in the medically induced coma. At this point, the patient is diagnosed as having SRSE. We estimate that there are 25,000 cases of SRSE in the U.S.1-3 each year. Currently, there are no therapies specifically approved for SRSE.
About SAGE Therapeutics
SAGE Therapeutics is a clinical-stage biopharmaceutical company committed to developing and commercializing novel medicines to treat life-threatening, rare central nervous system, or CNS, disorders. SAGE's lead program, SAGE-547, is in Phase 3 clinical development for super-refractory status epilepticus (SRSE) and is the first of several compounds the Company is developing in its portfolio of potential CNS medicines. SAGE's proprietary chemistry platform has generated multiple new compounds that target GABAA and NMDA receptors, which are broadly accepted as impacting many psychiatric and neurological disorders. For more information, please visit www.sagerx.com.
Various statements in this release concerning SAGE's future expectations, plans and prospects, including without limitation, SAGE's expectations regarding SAGE-547 as a treatment for SRSE, essential tremor and severe postpartum depression, statements concerning the potential safety and efficacy of SAGE-547 and durability of response, the potential importance and impact of the Phase 3 STATUS trial and the open-label expanded access protocol for SAGE-547, and whether the results from the ongoing Phase 3 STATUS trial together with other available clinical data for SAGE-547 will be sufficient to support submission of an NDA for this product candidate, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. In particular, it should be noted that there is limited data concerning the safety and efficacy of SAGE-547. These data may not be repeated or observed in ongoing or future trials involving SAGE-547 or SAGE's other product candidates. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, SAGE's ability to successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, SAGE's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, competition from others developing products for similar uses, SAGE's ability to manage operating expenses, SAGE's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, SAGE's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in SAGE's quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2015, as well as discussions of potential risks, uncertainties, and other important factors in SAGE's subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent SAGE's views only as of today and should not be relied upon as representing its views as of any subsequent date. SAGE explicitly disclaims any obligation to update any forward-looking statements.
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3 Novy J, Logroscino G, Rossetti AO. Epilepsia 2010; 51(2): 251-256.