TRVN - Notes from the Oct 2015 R&D Day by Trevena:
1) TRV027 in AHF:
a. New facts: not too much, but for me (I track only some of the cc’s): Ph2 study planned to complete in 2Q16; the aggregate endpoint for the ph2b is Dyspnia 5 day VAS AUC, 30 day mortality, 30 day rehospitalization for HF, 5 day worsening hearth failure, and length of hospital stay; and they provided the powering assumptions for each component.
b. Color: They explicitly mentioned in the charts that they understand the phenotype variability as an issue (what I have referred to as disease heterogeneity). My comment is that their recognition of that issue is a big risk reducer IMO.
2) TRV130 (oliceridine – IV opioid):
a. The hypoventilation was defined to be persistent lowered respiratory rate, lower respiratory effort or lowered blood oxygen – but what counted as lowered rate etc was physician choice. Note that CO2 was not a criteria for judging hypoventilation – but in answer to a question they said they were looking at possibilities for ph3.
b. They said they are looking at some potential additional trials – in patients for whom the advantages of their drug may be even better. It wasn’t precisely clear to me how this would fit into the ph3 program.
c. They haven’t yet talked to the FDA about the endpoints (presumably since they are still refining the analysis etc)
d. They have no plans to test their drug against Fentanyl (despite the fact that it is the drug of choice in the PACU – which is first place pain is controlled. So I do not really get this. E.g. how is the switch done today for Fentanyl to morphine as patient moves from PACU to normal hospital floor. Won’t they need data on the interaction between Fentynal and 130 as the switch is made?)
e. Trial site variability – they clearly worked hard to find trial sites which would allow specifying the surgical protocol (most hospitals specify the acceptable protocols – and thus there is large variability between hospitals).
f. Color: they had as one of their presenters the organization that designed their soft tissue trial and he clearly understood problems with trial design that I have never before seen any biotech directly address – e.g. increasing the “signal to noise” by reducing treatment variability and designing metrics that are more repeatable. Even more than in TRV027 they seem to understand what causes trials to fail and directly address them.
3) TRV734 (oral opioid)
a. From comments it is clear they just started shopping for a partner.
b. They do not intend to try to find their own anti-abuse system – since, for instance, many potential partners will have their own personal favorites.
