Update on AM-101 (aka Keyzilen)

I've attached the presentation from Auris Medical's "Key Opinion Leader" meeting held today (June 14). They seem pretty confident (though they were talking to investors....) and have officially named AM-101 as "Keyzilen".

There are four parts to the presentation. The first is an introduction; the second is a detailed discussion of the TACTT trials including endpoints required for regulatory approval; the third is a discussion by Hinrich Staecker about inner ear tinnitus; and the last is a market analysis.

The discussion of requirements for regulatory approval are interesting. They will need to show significant and clinically meaningful improvement over placebo in tinnitus loudness and the TFI for TACTT2. Also of note: the randomization was 3 to treatment for each 2 to placebo.

More comments later...

 

Sweet. Sound good keep us updated.

 

Based on the numbers in the PowerPoint, Auris Medical expects to generate drug revenues in the amount of $3000 an ear, not including ENT injection costs.

 

Does this mean AM-101 works?

 

Interesting presentation, so why they don't have any data on how many people got cured?

 

This 2015 article say:

"Auris is in late-stage trials of AM-101, a derivative of the anesthetic ketamine, which it hopes will dampen the aberrant signaling in the auditory nerve that is perceived as tinnitus. In a midstage trial, the drug, injected into the middle ear, was not more effective overall than a placebo. But a subset of patients whose tinnitus was caused by trauma or infection said the drug made the sound in their ears softer, less annoying and less disruptive of sleep."​

Investors appear to be cautious given the challenges. Auris Medical went public on NASDAQ in August at $6 a share, using the trading symbol EARS. The stock is now trading at about $4.

Keep an eye on that stock. I think it's at 4.75. If it gets about 7 people are starting to believe, but they also have a hearing loss drug. I heard the Department of Defense is a big investor, so that's hopeful.


http://www.nytimes.com/2015/01/10/b...cted-attract-drug-makers-attention-.html?_r=0

 

Just learned the ongoing clinical trial results: http://www.fiercebiotech.com/biotech/auris-medical-off-target-tinnitus-drug-study

 

Sheeeiiitt

 

Just to inform you that Auris medical just released a new fact sheet about Keyzilen:
http://aurismedical.com/images/auris/Fact_Sheets/Keyzilen-Fact-Sheet-September-2017.pdf

Also in attached file.

 

I'm a bit confused: I thought the trial didn't lead to good outcomes, but in the file you posted the graph seems to indicate a significant improvement at D90, even more with the high dose.

What am I missing?

 

That's very good info from them!

I just hope that this works also for severe tinnitus and they will try to test that.

 

I was one of the test subjects, first they gave me the test version where they did not know if it was the real medicine or placebo. Later on after the trial I received the real drug, sadly it did not work on me... but maybe it will work on one of you.

 

I've posted about my experience before in a different thread about AM-101, and I'm curious how they are interpreting the data to show that it improved tinnitus loudness.

After I had the first round of injections my tinnitus actually got worse, it was much louder than where it was initially.

Over the course of several weeks the tinnitus did decrease in volume, but only back to where it had been before I had the first injection.

I had the same experience after the 2nd round of injections, louder tinnitus after the injections and then back to where it was.

My tinnitus never improved beyond where it was before the trial.

I still have tinnitus today, and sometimes think it's a little worse. I use to wake up with a few seconds of silence, but that no longer happens. I also have developed consistent insomnia, can't sleep for more than a few hours because of tinnitus, since being in the trial.

Another important point is that 90 days of observing patient improvements is not long enough to determine if the drug works or not. They should monitor people for at least 6 months up to a year in my opinion.

I sincerely hope there is a treatment as some point in my life that is truly effective, unfortunately for me AM-101 is not the one.

 

@ryant, do you think that these increases could be connected with the healing time your tympanic membrane needs after each injection?

 

I’m not sure what caused the worsening of the tinnitus after the injection. Several other other people reported the same side effect.

 

I am asking only because it's normal to have a slight increase for a few days (even weeks) due to the nature of the procedure (conductive loss due to the membrane perforation).

If that was the case then probably we are talking about zero gains.

 

I thought I would actually post positive thread for once. I imagine you're all sick of my soul draining negativity. As dark and rainy as my world may be, there is one thing the gives me hope, and that is Keyzilen (AM-101).

The drug is currently in Phase 3 testing. It is a gel that when injected into the ear acts to suppress cochlear NMDA receptors that apparently play a role int he development of tinnitus from being acute to chronic. There are clinical trials in the US people ca take part in, but only with the first 3 months of your tinnitus. I kick myself sometimes because it means I could have stopped this during the summer when it was still "acute", but now its too late.

It does represent hope for the future though. This drug (as well as AM-111 for Meniere's Disease) could be the gateway to some kind of chronic tinnitus treatment. More importantly, it potentially means fewer chronic sufferers in the future. The animal trials apparently involved exposing mice to a loud ambulance siren for 45 minutes to induce tinnitus. My heart goes out to those mice, cured or not.

There link below has more information. I certainly hope this means for the rest of you, a cure is on the horizon at some point. I am skeptical i this condition can really be "cured" but I suppose suppressing the neurons needed to generate the noise is enough for me.

http://www.aurismedical.com/product-candidates/am-101

(No I am not an employee of the company. If I was I'm a pretty shitty PR guy)

 

Considering that AM-101 tried something very similar a year or two ago and failed, I don't think Keyzilen is going to be what we're looking for. Sorry...

 

Isn't Keyzilen just the name they gave AM-101?

 

Yes

 

??

People have been discussing AM-101 / Keyzilen here for several years with 2000+ messages in the thread (and it doesn't work for most of those who tried)

Sorry if I'm missing something, but why are you speaking about it like it's a new hope?

 

I'm new to tinnitus and newer to anything research related. I only recently heard about it.

 

Do you know that Keyzilen is only meant to be for acute, is it with certainty that it won't work for those who have had tinnitus a long time?

Also, the next results are expected in Feb 2018 - this could mean that this medicine will be on market by next year?

 

Oh man, AM 101 memories. I remember the car salesman pitch the site coordinator gave us when he heavily implied so many people were cured when given the real drug.

 

Is Am-101 only for acute tinnitus ? Or can it be helpful for chronic Tinnitus after 6 months ?

 

This - i.e. doing a prepping of the patients - is actually a huge problem for patient reported subjective trials. Otonomy suffered the same fate as AM-101 did (for TACTT2 in the US) with OTIVIDEX due to investigator introduced bias by letting patients know they think it works. It increases the placebo-response of the investigation making it harder to prove a significant difference between the placebo group and the group that received the actual drug. The consequence is that a trial may fail even though the drug is actually efficacious. At best, this causes the overall trial to be prolonged which is expensive for small pharma companies (as an example, Otonomy will now have to fork out around 10-13 million dollars to do a retrial of OTIVIDEX - which they expect the FDA will require); worst case, the overall trial fails and the drug never makes it to the market (which is sad when there are no existing drugs for a given condition). The problem of investigator bias was specifically referenced by Otonomy in relation to the US trial sites (not the European ones). In the case of OTIVIDEX in the US, the cause was both prior experience with the drug and a financial motivation of the study sites for participating/recruiting patients which the more academic study sites in Europe did not have. The interested reader can find some of the excerpts about that from the January 11th presentation by Otonomy (and this is not on the Internet - so, you can only read it here...).

The overall implication of stuff like "prepping the patients" may be that tinnitus population will have to wait additional years before standardized drugs hit the market; in some cases, a given small pharma entity may end up bankrupt causing lots and lots of knowledge and progress to go lost. This is a big deal and if I were a person suffering from tinnitus and had my life ruined from the constant ringing, I would be pretty upset about it...

Excerpt #1 (David Weber, CEO):

"And in working through that analysis as well as working with experts and patient reported outcomes and placebo response, what our review suggests is that the higher placebo response is due to increased expectation bias in the US trial. Now many of you may ask what is expectation bias? Basically, it is the expectation of investigators, patients (or both!) regarding the potential for that therapy to be effective. What is key here is that the difference between the AVERTS-1 and AVERTS-2 trials – that were identical protocols – is the study sites. We had previously ran clinical trials with the majority of these investigators here in the US – so they had direct experience with OTIVIDEX; they had an understanding of how that product worked compared to AVERTS-2 in Europe where we had not conducted any efficacy work before the AVERTS-2 trial. So as a result of that, what we’ve determined is that results of both study sites and clinical investigator experience, as well as in post-trial interviews with the investigators – both with the US investigators as well as with the European investigators, [point to] differences in the way they presented the trial to the patients in the way the enrollment process. Uhm, I think in Europe it was much more of an experimental based “we don’t know if the product works”; in the US, unfortunately, we believe that the investigators may have biased the patients by making comments about the prior positive experience."

Excerpt #2 (Kathie Bishop, Chief Scientific Officer):

"Uhm… but there were some factors that we found that probably contributed to the placebo response. One is that AVERTS-1 trial was conducted in the US on the background of the phase-II trial which was also conducted in the US. And although the phase-II trial just narrowly missed statistical significance on the primary endpoint, all clinicians and coordinators and people dealing with patients in the US generally felt like it was a successful trial. And what happens is they probably over-communicated that to patients coming into the trial – so the message was more along the lines of “this drug really works, you should come and be in this trial” rather than what happened in Europe where they had no previous efficacy experience and their message was much more measured being something along the lines of “this is an experiment – we don’t know whether the drug works, so come and be in this trial”. And that expectation bias and expectations about the efficacy of the drug got communicated to the patients probably contributed to that higher placebo-response."

Excerpt #3 (Paul Cayer, CFO):

"Yeah so… obviously a lot of it depends on the ultimate design and that’ll be part of the perspective we will provide later in the first quarter here. We can tell you from sort of the history now of doing the phase-IIb and the two phase-III’s which were all about the same scope. So assuming a scope that is similar to that – sub-15 million, sort of in the range of 10 to 13. That’s why very early as we are working through the revised plan and the [inaudible], we are very clear to say that we have the cash in hand to be able to get Ménière’s through the clinical development required for registration."

 

Received mail from Auris about post acute tinnitus.

Thank you for your inquiry. We have seen some evidence that Keyzilen may work in a post-acute setting (3-6 months from onset, potentially more). It should be noted that the 3 or 6 month definitions of acute/chronic are to some extent “lines drawn in the sand” – the time window for therapeutic intervention will probably depend on a number of factors, including severity of damage, triggering factor etc. and thus vary between individuals.

 

When do we find out about the results from the latest phase 3 trial when they changed their end points to measure efficacy?

Regarding the last comment, I wonder if even you had tinnitus for years if it would work?

 

Auris Medical to Host Key Opinion Leader Call Focused on Keyzilen® Tinnitus Program on March 5, 2018.
Yes, that is tomorrow.

 

I participated in the phase 3 trial. Got in contact with several other people who also participated in it.
As far as I know no one of us received any benefit from it.