Thoughts on Trevena’s painkiller TRV130

My friend, @beeps, shares a good read at SeekingAlpha with me and asks my thoughts. I’d like to talk about Trevena (NASDAQ: TRVN) and its lead product candidate, TRV130.

Trevena’s painkiller, TRV130, is a G protein-biased μ-opioid receptor agonist[1]. “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
constipation 3.9% 8.3% 16.1% 9.4%
dizziness 11.8% 47.2% 58.1% 43.8%
feeling hot 0 5.6% 12.9% 1.6%
headache 15.7% 19.4% 22.6% 25.0%
hyperhidrosis 0 8.3% 16.1% 3.1%
nausea 19.6% 55.6% 74.2% 59.4%
somnolence 7.8% 11.1% 12.9% 23.4%
vomiting 2.0% 27.8% 54.8% 35.9%

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.

[1] J Pharmacol Exp Ther. 2013, 344(3), 708-717.


5 thoughts on “Thoughts on Trevena’s painkiller TRV130

  1. Michael Webb 2015-03-20 / 16:55

    You make the statement: “Opioid-related adverse events were more frequently reported in the TRV130 group than in the morphine group” and then go on to contradict yourself.

    Phase 2 studies are designed to select the optimal dose to study in a registration format. Clearly the 2 mg dose of TRV130 was vastly superior to morphine in pain reduction and caused less respiratory depression which happens to be the most serious side-effect.

    Your blanket statement ignores the fact that in 5 of 8 side-effects listed the 2 mg dose of TRV130 performs better than morphine. Less constipation, nausea, sleepiness and vomiting. And fewer headaches.

    I suggest you look more carefully at the evidence you post before arriving at faulty conclusions.


    • yixi 2015-03-20 / 17:41

      Over the 48 hour study period, only the TRV130 3 mg group showed statistically superior analgesic efficacy compared to morphine, with a p-value of 0.014. The p-value of TRV130 2 mg vs. morphine was 0.48.

      Liked by 1 person

  2. tblew 2015-04-18 / 12:23

    you are correct that in stating it is questionable whether the therapeutic index of trv 130 is superior to that of morphine. furthermore, the company’s press release is misleading. The 3 mg trv 130 is superior in analgesia but only the 2 mg dose has ‘similar’ side effects to morphine. The 3 mg dose is clearly more toxic. Thank you. I appreciate your uncovering this info. I have been wondering about side effects since the phase 1 study showed trv 130 produced more dizziness than morphine and this was not reported by co. in its press releases.


  3. Rob 2015-08-04 / 22:41

    Couldn’t a doctor simply presribe an anti-nausea/vomiting drug to combat any of these side-effects?



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