Trevena Inc (TRVN)

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iwfal Member Level Tuesday, 11/01/16 06:00:43 PM
Re: None
Post #
205627
of 209318 Go
TRVN - Notes from their American Society of Anesthesiologists R&D day (it wasn't officially an R&D day - but was 2 hours long and 3 different non-TRVN MDs) on oliceridine.

The 3 MDs were a P&T Committee Member, a surgeon and a anesthesiologist (i.e. a good representation).

Notes, in no particular order, on things that I hadn't heard on a TRVN cc before:

1) All 3 MDs noted that the lower rate of non-respiratory side effects was the most important from a cost perspective because respiratory depression that adds meaningful cost is an infrequent occurrence.

1a) Obviously the biggest well tested factor in the human data is the lower rates of nausea and vomitting.

1b) Two of the 3 MDs clearly wanted to assume that the mouse data, showing much better intestinal motility than morphine, was also true in humans (although both caveated it with - we don't actually have human data).

1c) They gave specific reasons why it is helpful - and, for instance, showed that in current SOC it is standard to use a drug that decreases morphine induced ileus. (Note that in response to a question, TRVN answered that the existing ph3s do have a standard set of AEs, and ileus is on it, but they don't expect to hit stat sig because the treatment duration is so short.)

1d) Respiratory Depression data - they quoted a statistic of only about 100 lawsuits due to Respiratory Depression adverse outcomes over a decade. And they further noted that Respiratory Depression is one of those things that produces a moderate number of close, scary calls, but generally doesn't have longer impacts (there was a quote from one of the MDs that said they track the use of the opioid blockers and in his institution they use about about 5 per year - out of presumably 1000s of surgeries). Finally note that one of the MDs made a passing mention of respiratory depression impacting him due to middle-of-the-night calls.

2) P&T Committee decisions - they noted that in theory the P&T Committee is supposed to make decisions that save overall cost, but in practice they have a "siloed" budget and thus it is difficult to get new drugs onto pharmacy. Two of the MDs independently noted that to get a new drug approved an MD within the institution generally has to ask and then is often approved only provisionally until they can, in fact, show the savings elsewhere.

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iwfal Member Level Thursday, 07/07/16 10:37:02 PM
Re: Whalatane post# 202426
Post #
202444
of 209318 Go
Quote:
How do you feel about TRVN now, in July and around $6.80 ?


Well, the post to which you are responding gives a pretty good feel for my comments on their lead drug - and not much has changed since then. The only other comments would be on:

A) their oral agent (to avoid constipation) - but I don't have any particular insight into how well it will work efficacy wise (vs other oral opioids) and how much less constipation it creates vs the opioid adders that also work to reduce constipation. And, given the company silence on it, I assume it is just as addictive as a traditional mu opioid.

B) their pre-IND delta-opioid for migraine. Migraines seem a reasonable target for a delta opioid for several reasons, but there are still a lot of risks.

B1) The positives are:

B1a) It is known that delta-opioids, in animals, work well on hyperallodynia, but not on "acute" pain (typically meaning pain from acute injury). So migraine seems a reasonable target - but far from a sure thing.

B1b) One animal model of migraine, inducing Cortical Spreading Depression via nitroglycerin, does show efficacy from delta-opioids. However the model is, at best incomplete. CDS seems to be a good model for auras, but may not be great for the pain itself.

B1c) delta-opioids are free from many of the side effects of mu-opioids... (e.g. addiction and respiratory depression) if they can avoid the seizures (I think this is the least risky of the 'positives'.

B2) The negatives (aside from the risk to the positives) are:

B2a) delta-opioids seem to be something to which animals become very tolerant very quickly. This, again, makes migraine a good target since it would involve repeated acute treatments. Unlike, for instance, one of the delta-opioids that was tried in humans for RA and failed spectacularly.

All told, they have a pipeline. But all pain and two of the three are still very early on the risk burn-down.

FWIW.

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iwfal Member Level Tuesday, 05/17/16 07:14:05 AM
Re: poorgradstudent post# 201412
Post #
201422
of 209318 Go
TRVN
Quote:
I had expressed doubts about it due to the subtlety of the proposed mechanism, but would have liked to see a hint or two of efficacy.


As you probably remember, my doubts TRV027 were similar.

Quote:
What is the next milestone for the pain drug?


Start of ph3 trials (two efficacy, one safety) for TRV130 (Oliceridine). Virtually certain of meeting the primary endpoint (pain relief response vs placebo). But of course the more interesting endpoints are the secondary ones. Although I've long said TRV130 is a better drug it isn't so much better that it would obviously drive prescribing. Some of the concerns I've expressed over time are:

a) Not clear that they can easily claim both better pain relief and better nausea. Comment based upon their recent EoP2 CC: They seem to be choosing a pain endpoint for which they will be about the same as morphine (and thus better nausea and vomiting). Not clear to me that nausea/vomiting reduction will drive prescribing.

b) The respiration data for 130 in ph2 showed stat sig benefit vs morphine in events, but the advantage wasn't huge. And the clinical relevance of their ph2 endpoints wasn't completely clear (i.e. it was a technical metric vs a strong clinical one like respiratory rescue). Comment based upon the recent EoP2 CC: They picked a post hoc endpoint that, while still a technical metric (not a strong clinical one), shows much more dramatic effect (total time in respiratory depression) since morphine seems to not only cause more incidents, but the incidents also last substantially longer. It is post hoc (as they acknowledge), but the p value is very small. My personal opinion is that this might be a significant differentiator in prescribing since I suspect respiratory depression can drive hospital costs through longer stays and tighter care.

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