@attheedgeofscience believed this injection drug would be successful, he was wrong
Okay, so I have been checking in with TinnitusTalk a little more often than I would have under normal circumstances. Given the nature of the subject, my previous role in certain matters, and the fact that my name has been mentioned, I guess some kind of response is indicated.
It is correct that I assumed that AM-101 would ultimately prove to be successful (despite a less conclusive phase-II trial). There are a number of reasons for this, but, I do not wish to turn this into a whole essay, and so, I will limit myself to a few snapshots of my line-of-thinking in this. But firstly, I would like to mention that the full trial is not over yet (TACTT3 stratum A + B still awaits) - so to say that I am wrong is a little premature (but then again, accuracy of statements has never been the forté of the average member here). I should also mention that there are "other people" than just tinnitus sufferers reading this, and so, that is another reason why I do not wish to be too clear and exhaustive in my wording.
So what's the deal here? Well, I attended the two latest conference calls hosted by Auris Medical (the last one being the one held this past Thursday where the TACTT2 news were released). I also attended the latest conference call by Otonomy (for their Q2 2016 results). Given that they are both publicly listed companies, the presentations they make follow essentially the information released via their website (see attachment pdf-file).
Back in 2014, Prof. Marlies Knipper was part of a symposium hosted by Auris Medical. There were several different speakers; she was one of them. She brilliantly covered the science on cochlear tinnitus and the assumed mechanism of action of NMDA receptor antagonists (incl. details such as to how there is a difference between inner ear- and outer ear- hair cells; tinnitus being caused by inner ear hair cells - or so it is thought). In that presentation (which is about 15 minutes long), there is a "controversial" moment where she mentions that the animal studies conducted - and where efficacy was observed during a time window of days - would translate into the same drug being efficacious for up to several months (in humans). How that was determined, I do not know.
As for phase-II vs phase-III, I assumed that an improvement in terms of demonstrated efficacy would be shown - in part - because:
- The inclusion criteria (= the study population) would be better targeted (in phase-III vs phase-II which included idiopathic cases of tinnitus).
- Larger sample size (allowing for a better spread of various variables - including time of treatment after onset i.e. a better potential to have really early onset candidates).
- The phase-III study "survived" an interim assessment.
However, it turns out that in phase-III, a two week screening period was introduced. My understanding of this is that this essentially adds an additional two weeks to every candidates time of treatment (vs. onset). Clearly if tinnitus is time sensitive to treatment, then introducing a like-for-like two-week delay (vs. phase-II) is a pretty impactful variable (at least, in my opinion). This topic was touched upon (slightly) during the conference call:
So it is possible that the study failed to show efficacy not because of the science, but, because of the study design.
Now, I could go on and on about "this and that" and some other thing. But let's assume for a minute that the study actually will not pass (in the end). What then tinnitus community - what will you do? Back in October last year, when the AUT00063 QUIET-1 study failed, an announcement was made here on the forum:
Those who pay attention will notice that the info-sheet was downloaded an incredible +50,000 times. Compare that with the average attachment which typically is downloaded - on average - 10, 20, 30, or perhaps 50 times. Suppose back then that every person who downloaded the info sheet had also clicked our Trobalt campaign (which I was very much part of devising) or some other initiative - think about the massive amount of awareness there would now be. Well, opportunities come and go. And for the tinnitus community, they seem to mostly go.
All the best to everyone. And, on a very final note: many many thanks to Auris Medical for being a pioneer in the emerging field of inner ear otology.