Trevena’s painkiller, TRV130, is a G protein-biased μ-opioid receptor agonist. “G protein-biased” means that the compound promotes coupling of the μ-opioid receptor to G proteins, but not β-arrestins. The G protein pathway was associated with analgesia, while the β-arrestin pathway was associated with side effects such as respiratory depression and constipation.
Trevena believes that TRV130 could increase analgesia and reduce adverse effects versus morphine. The company is developing TRV130 for the management of acute postoperative pain.
In November 2014, Trevena announced positive top-line results from the Phase IIa/b study of TRV130 in acute postoperative pain following bunionectomy. The 3 mg dose of TRV130 showed statistically superior analgesic efficacy compared to the 4 mg dose of morphine. In addition, TRV130 showed trends of less respiratory depression than morphine.
However, Trevena shares were up only 3.71% on November 18, 2014. The Press Release said that TRV130 and morphine were both associated with opioid-related adverse events. The details could be found in the Form S-1/A filed on November 28, 2014. Opioid-related adverse events were more frequently reported in the TRV130group than in the morphine group.
|Placebo||TRV130 2 mg||TRV130 3 mg||Morphine 4 mg|
These data suggest that the therapeutic index of TRV130 is not superior to that of morphine and that the hypothesis of “G protein-biased ligand” may not be right. I don’t consider the upcoming Phase IIb results in acute postoperative pain following abdominoplasty as an attractive catalyst.
 J Pharmacol Exp Ther. 2013, 344(3), 708-717.