Trevena Announces Positive Top-Line Results From Phase 2a/b Study Of TRV130 In Acute Postoperative Pain

Trevena, Inc.

, a clinical stage pharmaceutical company focused on the discovery and development of G protein coupled receptor (GPCR) biased ligands, today announced positive top-line data from its randomized, double-blind, placebo- and active-controlled Phase 2a/b trial of TRV130 in moderate-to-severe postoperative acute pain. At doses of 2 mg and 3 mg TRV130 administered every 3 hours, the study achieved its primary endpoint of statistically greater pain reduction than placebo over 48 hours, successfully demonstrating proof of concept for TRV130. The trial was designed with key secondary endpoints to evaluate the differentiation of TRV130 from gold-standard morphine at a standard reference dose of 4 mg every 4 hours. Over the 48 hour study period, TRV130 3 mg every 3 hours showed statistically superior analgesic efficacy compared to morphine. Additionally, the 2 mg and 3 mg doses of TRV130 demonstrated statistically superior analgesic efficacy compared to 4 mg morphine in the first 3 hours of dosing, when study pain was most severe. For these doses, patients also reported maximum pain relief during the first dosing period that was statistically superior compared to morphine. Notably, in this study TRV130 at 2 mg and 3 mg demonstrated similar tolerability to morphine 4 mg over 48 hours. TRV130 and morphine were both associated with opioid-related adverse events, including dizziness, headache, somnolence, nausea, vomiting, flushing, and itching. “The data from this trial are impressive, suggesting that TRV130 may offer a superior product profile versus morphine, which frequently causes dose-limiting adverse events and often fails to fully manage post-surgical pain,” said Lynn Webster, M.D., past president of the American Academy of Pain Medicine. “Importantly, the study data demonstrate that treatment with TRV130 significantly improved analgesia versus a standard dose of morphine particularly in the early hours after surgery, when pain levels are at their highest. This increased efficacy was achieved with tolerability similar to morphine over the study period. TRV130 may therefore represent an important advance in pain management.” Study Results Success on primary endpoint: Doses of 2 mg and 3 mg of TRV130 at 3 hour intervals achieved a statistically significant reduction in pain intensity difference from placebo over 48 hours, measured as the time-weighted average change in pain score (TWA0-48). At 2 mg, TRV130 reduced average pain score (LS mean change in TWA0-48) by 1.4 points (p=0.0024 vs. placebo; all p-values 1-sided). At 3 mg, TRV130 reduced LS mean TWA0-48 by 2.4 points (p<0.0001 vs. placebo). Baseline pain rating was approximately 7 out of 10, a pain level considered severe. TRV130 achieved a reduction in mean pain intensity of up to approximately 6 points, with notable efficacy at 5 minutes, the first pain intensity assessment after dosing. Over 48 hours, 3 mg of TRV130 at 3 hour intervals achieved a statistically significant reduction in pain intensity difference from 4 mg morphine at 4 hour intervals, reducing average pain score (LS mean change in TWA0-48) by 1.0 point vs. morphine (p=0.014). Morphine reduced LS mean change in TWA0-48 by 1.3 points vs. placebo (p = 0.0023). When study pain was most severe, during the first 3 hours after the initial dose, TRV130 at 1 mg, 2 mg and 3 mg showed a statistically significant reduction in pain (TWA0-3) vs. placebo (LS mean change -1.0, -2.4, and -3.0 respectively; p = 0.021, p < 0.0001, and p < 0.0001, respectively). In addition, TRV130 at 2 mg and 3 mg showed a statistically significant reduction in pain vs. 4 mg morphine during this time (LS mean change: TRV130 2 mg -1.2 vs. morphine, p = 0.0029; TRV130 3 mg -1.8 vs. morphine, p < 0.0001). Consistent with these findings, more patients reported statistically greater peak pain relief during the first dosing period for 2 mg and 3 mg TRV130 compared to 4 mg morphine (p = 0.005 and p < 0.0001 for TRV130 2 mg and 3 mg vs. morphine, respectively). Complete pain relief during this period was reported in 13%, 31%, and 52% of patients receiving 1 mg, 2 mg, and 3 mg TRV130, respectively, compared to 0% and 8% for patients receiving placebo and 4 mg morphine, respectively. Adverse events associated with TRV130 were largely opioid-related; the most frequent reported events were dizziness, headache, somnolence, nausea, vomiting, flushing, and itching. Adverse effects were generally dose-related. No serious adverse events were reported in any study group. Tolerability for 2 mg and 3 mg TRV130 over the full 48 hours of dosing was similar to morphine. Rescue medication (acetaminophen or ketorolac) was used in all groups. Full results will be presented at a future scientific conference or in a journal publication. “The results from this trial support the potential of TRV130 to provide more rapid, reliable, and powerful pain relief than may be achievable with currently used opioids,” said David Soergel, M.D., senior vice president of clinical development at Trevena. “In this study, the magnitude of efficacy associated with TRV130 suggests it may be able to relieve the most severe types of pain, for which effective therapies are lacking. We look forward to building on these results with an upcoming Phase 2 trial in soft-tissue surgery patients and preparing for Phase 3 development.” “The positive data from this study represent a significant achievement for both the TRV130 program and our biased ligand platform,” said Maxine Gowen, Ph.D., chief executive officer of Trevena. “The trial results, including the striking level of analgesic efficacy achieved using an FDA-recommended endpoint for registration, provide us with a wealth of information that will enable a robust and efficient Phase 3 development program for TRV130. The data also provide further evidence that Trevena's novel, proprietary platform can deliver differentiated drug candidates with impressive clinical performance that may improve the current standard of care.” Study Design The Phase 2a/b study was a multicenter, randomized, double-blind, placebo- and active-controlled, multiple dose, adaptive study in 333 women and men undergoing a primary unilateral first-metatarsal bunionectomy surgery at four centers in the United States. Patients were randomized after surgery to receive TRV130, morphine or placebo to manage their pain. Pain intensity was measured using validated numeric rating scales at multiple time points up to 48 hours; based on these scales, analgesic efficacy was assessed as a time-weighted average change over 48 hours, an FDA-recommended endpoint. The study was conducted in two parts, with the goal of providing information on dose- and interval-ranging and furthering the differentiation of TRV130 versus morphine. In Part A, a pilot phase, patients were randomized to receive one of 4 doses of TRV130 (1 mg, 2 mg, 3 mg, 4 mg), morphine, or placebo, all given at four hour intervals. In Part B, the trial's adaptive phase, 8 cohorts were randomized successively to one of two adaptive doses of TRV130 given every 3 hours, morphine, given every 4 hours, and placebo in a double-blind, double-dummy fashion. In Part B, doses of 0.5 mg, 1 mg, 2 mg, and 3 mg TRV130 were evaluated. 141 patients were treated in Part A, and 192 patients were treated in Part B. Conference Call and Webcast The company will host a conference call and webcast to discuss the top-line results of the study. Slides will be available on the Investors section of the Trevena website at www.trevenainc.com. The webcast will be available for replay for 7 days. Date: Monday, November 17, 2014 Time: 5:00 p.m. (EST) Telephone Access: (855) 465-0180 (U.S. and Canada) International: (484) 756-4313 (International) Conference ID: 36872822 Online Access: http://www.media-server.com/m/p/nmvzazsq