Trevena Announces Positive Results from Phase 2b Study of TRV130 in Acute Postoperative Pain

Trevena, Inc.

, a clinical stage pharmaceutical company focused on the discovery and development of biased ligands targeting G protein coupled receptors (GPCRs), today announced positive data from its randomized, double-blind, placebo- and active-controlled Phase 2b trial of TRV130 in moderate to severe acute postoperative pain after abdominoplasty surgery. The study achieved its primary endpoint of statistically greater pain reduction than placebo over 24 hours. In addition, TRV130 was superior to morphine in pre-specified secondary measures, exhibiting significantly reduced nausea, vomiting, and hypoventilation events. "The data from this trial showed that TRV130, when given on-demand, matched morphine efficacy for pain relief with a markedly improved safety and tolerability profile," said Neil Singla, M.D., chief scientific officer of Lotus Clinical Research and lead investigator of the study. "The challenges of safely and adequately titrating morphine are well recognized, and these data suggest that, if approved, TRV130 may provide a better option than currently available opioid analgesics." In the trial, two regimens of TRV130 were tested: the first consisted of a 1.5 mg intravenous loading dose with 0.1 mg self-administered on-demand doses as often as every 6 minutes (together referred to here as "TRV130 0.1 mg") using a patient controlled analgesia (PCA) device; the second consisted of a 1.5 mg loading dose with 0.35 mg on-demand doses (together referred to here as "TRV130 0.35 mg") using a PCA device. A commonly used morphine PCA regimen was also tested, consisting of a 4 mg loading dose with 1 mg on-demand doses. Placebo was administered as a loading dose and on-demand doses that were volume-matched to the active regimens. Study Results Efficacy • TRV130 demonstrated statistically significant pain reduction compared to placebo and comparable efficacy to morphine. The TRV130 0.1 mg regimen reduced average pain scores (LS mean change in time-weighted average over 24 hours) by 2.3 points (p<0.0001 vs. placebo). The TRV130 0.35 mg regimen reduced average pain scores by 2.1 points (p=0.0003 vs. placebo), similar to morphine, which reduced average pain scores by 2.1 points (p=0.0001 vs. placebo). • TRV130 provided rapid reduction in average pain scores, consistent with the previous Phase 2 trial where TRV130 showed more rapid onset of meaningful pain relief than morphine. • Rescue analgesic use was similar for both TRV130 and morphine, and less than half the rate of rescue analgesic use for placebo. The proportion of patients using rescue analgesic was 64% with placebo, 31% with TRV130 0.1 mg, 21% with TRV130 0.35 mg, and 25% with morphine (post hoc p<0.0005 for all three active arms vs. placebo). Safety and tolerability • In this study, the TRV130 groups had a significantly lower prevalence (percentage of patients) of hypoventilation events (a measure of respiratory safety), nausea, and vomiting than the morphine group (post hoc p<0.05 for both TRV130 regimens vs. morphine). Placebo TRV130 0.1 mg TRV130 0.35 mg Morphine Hypoventilation 10% 15% 31% 53% Vomiting 8% 15% 15% 42% Nausea 18% 41% 46% 72% • Adverse events associated with TRV130 were largely opioid-related; the most frequently reported events were nausea, vomiting, hypoventilation and headache. Opioid-related AEs were generally less frequent in the TRV130 groups compared to morphine. No drug-related serious adverse events were reported in the study. Total TRV130 use in the study was similar for the two TRV130 regimens with mean cumulative doses of 7.6 mg and 5.4 mg for the TRV130 0.1 mg and TRV130 0.35 mg regimens, respectively. The mean cumulative dose of morphine was 26.3 mg. Full results will be presented at a future scientific conference or in a journal publication. "The positive data from this study continue the impressive accumulation of evidence suggesting meaningful differentiation of TRV130 from morphine," said Maxine Gowen, Ph.D., chief executive officer of Trevena. "The goal of new analgesic drug discovery has long been the provision of more powerful pain relief with reduced opioid-related adverse effects. We believe the Trevena biased ligand platform has delivered this profile in TRV130 and we look forward to starting Phase 3 development in early 2016." Study Design The Phase 2b study was a randomized, double-blind, placebo- and active-controlled, multiple dose, adaptive study in 200 patients undergoing abdominoplasty surgery at a single center in the United States. At baseline, patients had a mean baseline pain score on the numerical pain rating scale (NPRS) of 7.7 out of 10, which is considered severe pain. Pain intensity was measured using validated numeric rating scales at multiple time points up to 24 hours. All study arms used a flexible dose, PCA administration regimen intended to optimize treatment and reflect the as-needed dosing most commonly used with post-operative opioid analgesics. All regimens were blinded and volume-matched, and consisted of intravenous loading doses followed by patient-controlled intravenous doses with a 6 minute lockout period after every on-demand dose. Patients were assigned randomly to post-operative regimens of TRV130, placebo, or morphine, in a 2:1:2 ratio respectively, beginning when post-operative pain became moderate or severe in intensity and continuing for 24 hours thereafter. Rescue analgesics were available as necessary for patients whose pain was not adequately treated by TRV130, morphine, or placebo; first line rescue was oral ibuprofen and second line rescue was oral oxycodone. A standard methodology was used to avoid including effects of rescue analgesics on pain intensity measures: an unscheduled pain intensity assessment was made before rescue analgesic dosing, and this value was used instead of the scheduled pain intensity values until the end of the study. In this trial, respiratory safety was measured as hypoventilation events, defined as clinically apparent and persistently decreased respiratory rate, respiratory effort or oxygen saturation. In practice, such events can result in interruption of opioid analgesic administration or, if unrecognized and if additional opioids are administered, to more serious consequences. A pre-specified interim analysis was conducted after enrollment of 100 patients to evaluate opportunities for studying additional regimens of TRV130, after which the on-demand dose of TRV130 was increased to 0.35 mg for the remaining portion of the study. Conference Call and Webcast Date: Monday, August 31, 2015 Time: 5:00 p.m. (EDT) Telephone Access: (855) 465-0180 International: (484) 756-4313 Conference ID: 26412950 To access the live audio webcast of the presentation and the slides, please visit the Investor Presentation section of the Company's website. The webcast will be available for replay for 7 days.