Mu Opioid Biased Ligand Demonstrated Increased Analgesia with an Improved Safety/Tolerability Profile Compared to Morphine
KING OF PRUSSIA, PA, May 2, 2014 – Trevena, Inc. (NASDAQ: TRVN), a clinical stage pharmaceutical company focused on the discovery and development of G protein coupled receptor (GPCR) biased ligands, announced that data from the Company’s Phase 1b trial of TRV130, a small molecule G protein biased ligand at the mu-opioid receptor, are being presented today in a poster session at the American Pain Society Annual Meeting in Tampa, Florida. In the study, TRV130 was generally well tolerated and produced greater analgesia compared to morphine with less reduction in respiratory drive, less vomiting, and less severe nausea in healthy subjects. TRV130 is in development as a first-line treatment for patients experiencing moderate to severe acute pain where intravenous administration is preferred.
“The data to be presented today provide early proof-of-concept for TRV130, suggesting that when compared directly to morphine, the biased ligand’s selective signaling may allow for better pain control, with less of the dose-limiting adverse events associated with current opioid treatments” stated David Soergel, M.D., senior vice president, clinical development at Trevena. “These results suggest that TRV130 could be a meaningful advance in the treatment of pain after surgery and provide a strong rationale for continued development.”
The results will be presented in a poster entitled, “TRV130, a novel biased opioid ligand, elicits increased analgesia with reduced adverse effects compared to morphine in healthy volunteers.” The randomized, double-blind, placebo-controlled, 5-period crossover study enrolled 30 healthy adult males. Subjects were administered 1 of 5 treatments in each period: 1.5 mg, 3.0 mg, or 4.5 mg of TRV130 via intravenous administration, 10 mg morphine or placebo. The objectives of the trial were to evaluate the safety and tolerability of TRV130, the analgesic effects of TRV130 using the cold pain test vs. placebo, compare TRV130 to morphine and to placebo, evaluate the pharmacokinetics of TRV130 and evaluate the effect of TRV130 on responses to the Drug Effect Questionnaire.
As measured by the cold pain test, TRV130 at 3 mg and 4.5 mg increased analgesia with a more rapid onset of action, superior analgesic effect, and similar duration of action compared with 10 mg morphine. In addition, at the 3 mg and 4.5 mg TRV130 doses, more subjects doubled baseline cold pain test latency and achieved maximum cold pain test latency of 180 seconds. In addition to increased cold pain test efficacy, TRV130 produced less reduction in respiratory drive as compared to morphine, as measured by the ventilatory response to hypercapnia.
“The impressive results of this trial demonstrate the clinical translation of our proprietary biased ligand platform into a potential new and differentiated pharmacotherapy for the treatment of moderate to severe, acute postoperative pain,” stated Maxine Gowen, Ph.D., chief executive officer of Trevena. “Based on this strong data set, we are advancing the development of this program. We recently initiated a Phase 2a/b trial of TRV130 in bunionectomy patients, and plan to launch a second Phase 2 trial of TRV130 in soft tissue surgery patients in the fourth quarter of this year.”
About TRV130 and Acute Pain
The mu-opioid receptor is a well-established target for analgesics such as fentanyl and morphine, which are unbiased mu-opioid agonists. TRV130 activates the mu-opioid G protein pathway, associated with analgesia, and inhibits the beta-arrestin pathway, which, in preclinical studies, was associated with respiratory depression and constipation. The preclinical pharmacology of this novel molecule has been previously published in the Journal of Pharmacology and Experimental Therapeutics, with data suggesting that TRV130 is powerfully analgesic with an improved safety and tolerability profile when compared directly to classical opioids such as morphine. In the first clinical study of TRV130, which was published in the Journal of Clinical Pharmacology in March of 2014, TRV-130 had robust CNS activity and was well tolerated in healthy volunteers. .
Trevena anticipates that the initial market opportunity for TRV130 will be in this acute care hospital setting, with a focus on postoperative pain. Dosing of mu-opioid agonists, the most effective class of analgesics currently available, is limited by severe side effects such as respiratory depression, nausea and vomiting, constipation and postoperative ileus. Trevena believes that TRV130 may offer improved analgesia with reduced incidence and severity of these on-target adverse effects, which could help ease the suffering and burden of care for post-surgical pain. In national surveys, approximately 50% of surgical patients report moderate or severe pain while in hospital despite the use of opioid analgesics, and the cost impact of opioid-related adverse effects in US hospitals is estimated to be up to $5 billion annually.
Trevena, Inc. is a clinical stage biopharmaceutical company that discovers, develops and intends to commercialize therapeutics that use a novel approach to target G protein coupled receptors, or GPCRs. Using its proprietary product platform, Trevena has identified and advanced three differentiated biased ligand product candidates into the clinic – TRV027 to treat acute heart failure, TRV130 to treat moderate to severe acute pain intravenously, and TRV734 to treat moderate to severe acute and chronic pain orally. Trevena also plans to advance additional product candidates in its portfolio, including a preclinical program focused on central nervous system indications.
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