Update on AM-101 (aka Keyzilen)

:'(

 

I'm not surprised. This line of research just isn't showing potential.

 

Fail. Sigh.

https://www.marketwatch.com/story/a...innitus-trial-missed-goals-2016-08-18-7913351

 

This is an old paper, but the product hasn't improved much.

 

Sure is - bad on me. I should've checked that.

 

...the clue was in 2016

 

So, for those interested in the Keyzilen-update from today, topline results for TACTT3 were not released. Instead, half of the roughly 50 minutes presentation featured Dr. Michaelides who was a principal investigator in the TACTT2 trial (i.e. the first of two phase-III trials that saw the publication of results in the Summer of 2016). There wasn't really anything newsworthy about the update today, but Dr. Michaelides did present a couple of slides that on a participant-level basis indicated Keyzilen works:



The graph shows that of the eight enrolled patients which he treated himself, those who got the study drug (the green dots), a reduction in the perceived loudness and the TFI score was observed. Those who got the placebo (the red dots), did not experience such an improvement.

Now, as there wasn't any concrete data presented on TACTT3, there isn't really much point in trying to speculate on the final outcome (data should be released soon enough, anyway). And yet, based on the totality of the information presented during the call today, it would seem that AM-101 is likely to make it to the market eventually. The reason for that is because, for the subgroup of participants who enrolled because of otitis media, confirmatory testing will be done independently (if the overall trial doesn't meet its endpoint for TFI). And since it is known that this subgroup did well already in TACTT2, then it seems likely that Keyzilen will end up being indicated for such patients as a minimum (i.e. those with tinnitus as a result of middle ear infections). In addition, the AMPACT study showed increased benefit for those who did three rounds of injections (with 3 injections in each round). And so, all-in-all, it looks like there is enough data to suggest that NMDA-receptor approach works.

And lastly, I realize there are a number of people on TinnitusTalk who participated in the trials and who felt they got no benefit. But, I don't recall if the trial remained blinded indefinitely. For sure, I recall that the QUIET-1 study participants were eventually told whether they received placebo or the study drug, but I forgot the details on AM-101. But clearly if the AM-101 was blinded all the way, then it is difficult for anyone to say on a case-by-case basis whether AM-101 works or not.

The above are of course my own opinions (for what they are worth).

 

Sorry , but I am Dumb... I Did not understand the middle part... What about noise induced tinnitus? Any hope for that?

 

We shall see. There was a 2nd subgroup (those with severe tinnitus) who benefitted. I think AM-101 will end up working for both acoustic trauma and otitis media, but only during the acute stage (possibly very acute stage) – this has already been confirmed as the stratum B treatment arm (i.e. who with post-acute tinnitus) was reduced from patient intake up to 12 months chronicity down to six months (because there was no efficacy in the former category). Early treatment intervention possibly followed up by additional rounds of treatment seems to be what works...

 

Be IT acute or or chronic IT still gives hope. Tnx for informing us

 

There is no doubt that there is a significant market potential for even acute tinnitus (reflected by the unmet need, in general). Some 250,000 ears are in scope each-and-every year for the US market alone:



And believe it or not, but physicians are frustrated (almost) as much as patients. It was clear from the presentation by Dr. Michaelides that a treatment would be welcomed by the ENT community...

 

That's $3,000 per ear if I'm doing the math right...

 

I am sorry, but who really believes that am-101 can still be efficient now? I have been following this for a while and I think if you look at all the experiences (on and off this board) with AM-101, they all tend to skew towards the (at best neutral), and sometimes even worse. I think that maybe 10-20% of the people that i read that did this had good experiences, and the other odd 80%, had neutral or negative experiences.

How come everyone is all of a sudden so enthousiastic about this again? Did i miss something in the last year?

 

I agree that the self-reported AM-101 experiences we have seen on TinnitusTalk have not been overwhelmingly positive, but... here is the thing. During the update yesterday, Dr. Elias Michaelides (professor and director of clinic), shared his experience with AM-101 from his side of the table (and not the patient perspective). As an investigator of the trial, he screened 20 patients but enrolled just eight in the end:



The reason 12 potential patients were not enrolled was because they did not fit the patient profile required for the trial – which – included having a "clean" case of acoustic trauma (and not secondary trauma in someone with existing tinnitus). This is what an experienced investigator would know to look for (to ensure that such patients do not make it into the trial). Study sites with less experienced staff may not have that kind of expertise and also, there are definitely people who made it into the AM-101 trial who knowingly lied about their chronicity and/or etiology when they enrolled:

We can only speculate how big a problem "lying candidates" might have been. Remember: tinnitus is a subjective condition that no one else can see, and so, the patient has the upper hand when it comes to conveying information about things like onset of tinnitus and what caused it in the first place. It is known that those study sites with a larger intake of patients had a better outcome than those with fewer patients. Regardless, here is another slide by Dr. Michaelides that shows how a placebo-patient vs. a study drug-patient perform (when enrollment is "done right"):



Should the trial ultimately fail, it is not inconceivable that the tinnitus community is partially to blame. Something to thing about...

 

@attheedgeofscience Thank you very much for explaining this so clearly and succinctly. I really hope that with this new study they where able to get better data. If it would help anyone I would be the first to jump for joy. We all just need to find something that works. And if this is just for the acute cases, that is fine. That’s only one part of the bigger picture solved, but also a very important part.

 

@attheedgeofscience
Everyone participating in that trial received a second round of an open label dosage. This, for those who doesn't know it, is that they provided subjects with the real drug. No room for placebo. From all the people I know who participated in the trial, even having been in the time frame they considered the drug to be potentially effective, no one experimented any kind of relief.

 

I'll never get that part about acute and chronic tinnitus. When it's acute you never know whether it'll become chronic or not and also, to me it seems the problem area ought to be the same. (Though I understand that there are different opinions there, brain vs ear and so on).

What I'm saying is, that if you treat "acute" tinnitus, how do you know it's actually the medication that works or the acute T fading by itself?

 

Good question, I had temporary tinnitus that lasted days before it disappeared before it eventually became chronic

 

Can somebody tell me why the tinnitus scores started off higher than the placebo?? Please don't tell me it is some kind of marketing gimmick to make it seem better than it really is like a sale at a clothing store.

 

hi joe,
what are your experiences during the trial? has your tinnitus got a spike?

 

AMA -101 is DEAD people it’s 2018!!! Don’t waste your hope on this study anymore. It was a valiant attempt. NEXT...

 

Pretty much exactly this. I don't know why people still care about this.

 

There was a pretty large thread on this forum with people that went through the trials (myself included).

 

I was informed after the AM-101 trial was concluded. Turns out I did get the active drug on the first round. I remember after the first round I got on the plane and as soon as the cabin pressurized my ears drained. I doubt that had any impact as they give it over three days and put a lot of the viscous drug in there.

I think the window of opportunity between 'acute' and 'chronic' tinnitus is likely much shorter than previously thought.

 

First off, it is AM-101 not AMA-101. Second, it's odd that you are saying this in response to a post I made almost 2 years ago. Finally, your point would be much better made - at least about Auris as a company - by pointing out that Auris is in danger of being de-listed from the NASDAQ and is holding an "Extraordinary General Meeting" of shareholders tomorrow to talk about undertaking some stock manipulation to attempt to satisfy the NASDAQ. You might also point out that if they had good news on TACTT3, it would have been in their interest to reveal that in the meeting last week (i.e. ahead of the 'extraordinary' meeting). It is of course possible that they haven't finished analyzing the data (or will reveal good news tomorrow). However, they did have time to cherry pick some special cases, and they have a habit of "creative" interpretation of their data....

 

I agree. I'm sad to hear this. AM101 may be a bust, but Auris was dedicated to investigating inner ear disorders.

For me, AM101 did seem to get rid of the fleeting tinnitus I would occasionally get (it came back a year later), but that's about the only benefit.

 

Howcome all of your posts are written like bad Twitter posts? It's like you add absolutely nothing to the conversation and just inject negativity into pretty much all threads you make contact with.

Let them do their research and let people keep their hope.

 

What about their AM-111 product, this would greatly assist tinnitus drawn on by hearing loss??

 

Auris Medical Holding (EARS) Says TACTT3 Clinical Trial with Keyzilen Did Not Meet Primary Endpoint

Auris Medical's Keyzilen flunks second late-stage tinnitus study; shares down 30% after hours

 

I am getting a ketamine infusion tomorrow. Maybe the ketamine works better IV than through the eardrum?