Update on AM-101 (aka Keyzilen)

[Mic]

Hmmm... not sure I fully agree with this. The general consensus/assumption amongst the members of this community seems to be that, in the case of Auris Medical, it is the drug itself which is at fault. What if in fact it is the not the drug that is at fault, but the inability to demonstrate efficacy due to factors such as:

• Obtaining a standardized patient profile which specifically matches the etiology dimensions required
• Clinical trial design
• Placebo response
• Efficacy variables available for assessment (e.g. how to rate an improvement such as via MML and/or the TFI)

If the drug is at fault, then it's easy enough: wait for the next big thing to hit the news. But... if other factors are at play, then those "next big things" to come along may well be subject to the same problems as we have seen with AM-101. And history will repeat itself, in that case.

Well... in the 'dark scientific age' we live in, pre-clinical trails on animals who can't tell us if they have tinnitus, nor if any intervention is effective in supressing it, are considered common practice in drug discovery. Take in account that a substantial part of medicines now in use are discovered by sheer luck... hell we even don't now exactly why a common painkiller like paracetamol acts on the biology of humans... we learn by trail and error... not by reasoning and developing drugs with science based methods...

This is, from my point of view, the core reason why Auris failed, and many others will fail in the future, till some pharma company wins the lottery by pure luck.

In addition, the consistent inability to bring a drug to market is not going to please investors. Simply put: why risk your investment when you can place your money earning the same ROI with a lower risk somewhere else? So, results such as those seen in the AM-101 trial or the QUIET-1 study could have wider implications.

Public health related matters should be considered common goods. Approaching drug discovery with capitalistic ideas leads to corruption of goals. Scientist won't work for proving the efficacy of new drug but to save the earnings of shareholders. This is why so many ineffective garbage (like many anti-depressants) or dangerous drugs (like our beloved Retigabine) is still pushed to the market.

And lastly, if Auris Medical would have had more success early on with AM-101 and AM-111, they could have become the experts in the field by cementing their market position against competitors. This could have led them to earn revenue needed for further research and eventually become the experts and develop additional therapies down-the-road. Now Auris Medical looks like a company struggling for survival and perhaps this may end up with the tinnitus community losing out on a lot of progress and collateral damage.

No, they would first of all protect their 'discovery' by patents and stop others from using their data to further improve efficacy. Second they would build upon minor improvements on the same half proven mechanism of action to extend patents and generate more revenue. It's like cars. The past 100 years every car manufacturer played for safe by improving little and shoving up the same in a new package again and again...till...

Musk... we need many more Musks... visionairs who aren't afraid of taking risks and are considering money as an instrument... not the goal of our existence...

 

[Pleasure_Paulie]

Take in account that a substantial part of medicines now in use are discovered by sheer luck... hell we even don't now exactly why a common painkiller like paracetamol acts on the biology of humans... we learn by trail and error... not by reasoning and developing drugs with science based methods...

Well coming from somebody who works in pharmaceuticals, this is simply not the case for majority of medications, while it may be true for Panadol. They start with a firm scientific hypothesis as I suspect Auris medications did. There is a lot of smart people working very very hard on drug development. Yes, some drugs do yield benefits to other conditions in phase 3 which later often becomes its primary use but it's extreme to say most drugs were discovered this way. In fact some of the new developments in drug discovery using machine learning is going changing a lot moving forward.

Approaching drug discovery with capitalistic ideas leads to corruption of goals. Scientist won't work for proving the efficacy of new drug but to save the earnings of shareholders. This is why so many ineffective garbage (like many anti-depressants) or dangerous drugs (like our beloved Retigabine) is still pushed to the market.

That is idealistic. We would not have half our medications if it wasn't for big Pharma and when we have treatment for tinnitus it will probably be by big Pharma due to the gap in the market currently and profit potential. People hate on big Pharma, that is until one of the drugs saves a loved one or helps you personally. Yes, some of their behaviour is unethical; I'm looking at you Valent pharmaceuticals!

Tobalt was innovative and revolutionary and helped many people with Epilepsy that did not respond to other meds. I'm confused, you're angry at GSK for getting this to market, yet it's one of the few drugs that helped tinnitus sufferers? Yes it's safety profile was poor, so GSK did the correct thing and removed it from shelves. Plus this design has prompted other companies to build upon this innovation.

No, they would first of all protect their 'discovery' by patents and stop others from using their data to further improve efficacy. Second they would build upon minor improvements on the same half proven mechanism of action to extend patents and generate more revenue. It's like cars. The past 100 years every car manufacturer played for safe by improving little and shoving up the same in a new package again and again...till...

And they have a right to protect their patient. If you spent 10+ years and billions in r&d would you not protect this? Pharmaceuticals is not at all like cars, changing and finding new compounds and clinical testing is very diffident from changing the design or engine of a car. And the cost is not be comparable at all.

Musk... we need many more Musks... visionairs who aren't afraid of taking risks and are considering money as an instrument... not the goal of our existence...

You've been had. Musk is a marketing genius and everything he does is about building the brand equity of his companies and his own name through brilliantly orchestrated stunts. His companies must run at a profit just like others to exist. He does not run charieties.

 

[Contrast]

I think Auris Medical has an problematic model of tinnitus, it is probably not generated within the auditory nerve.
NMDA blockage prevents more hair cell death from occurring, that explains why it helps tinnitus and excelled to Stage 3 trials

Therefore AM-101 could actually be acute hearing loss treatment based blocking NDMA to save hair cells from additional damage in cases where NMDA receptors add insult to injury after acoustic trauma

I agree with everything about the part stating "aberrant excitation of the audiotory nerve that is perceived as tinnitus" The auditory nerve itself is not generating the tinnitus signal, it's in the brain even in acute phases. If I understand correctly it is the Dorsal Cochlear Nucleus.


The central gain model is here I posted it a many times
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208401/
In a nutshell hearing loss causes less input from the audiotory nerve (not more) + higher brain functions compensating is the cause of tinnitus.

This explains why all forms of hearing loss from SNHL, middle ear surgery to ear plugs and ear wax have potential to lead to tinnitus. Anything that deprives the auditory nerve or even parts of the audiotory brain can cause tinnitus if one subscribes to central gain model. I don't think that is the case for the NMDA model of tinnitus

It's a shame there trial failed though, it would have helped acute sufferers

Unless they have a way to explain how ear plug experiments and ear wax can give healthy hearing people tinnitus the NMDA model of tinnitus is missing something and central gain model adds up a lot more. Then again I am just a mentally ill person on a tinnitus forum and not a researcher.

I am just confused why there are two models of tinnitus that contradict each other and only one holding up.

If there is something I am missing can someone please help me. I actually care about being less wrong

 

[ChrisBoyMonkey]

It is obviously a marketing video, but with a very hopeful claim we all long for.

 

[RichardGuy]

It is obviously a marketing video, but with a very hopeful claim we all long for.

I'm trying so hard not to be pessimistic, but she very obviously tries not to say "I don't have tinnitus anymore" just "I'm pretty sure I don't." On top of that, it sounded so scripted it may as well have come straight from Microsoft Danielle.

 

[AfroSnowman]

I'm trying so hard not to be pessimistic, but she very obviously tries not to say "I don't have tinnitus anymore" just "I'm pretty sure I don't." On top of that, it sounded so scripted it may as well have come straight from Microsoft Danielle.

Scripted and poorly acted for sure, but I'd take what she described as an outcome everyday of the week and twice on Sundays

 

[RichardGuy]

Scripted and poorly acted for sure, but I'd take what she described as an outcome everyday of the week and twice on Sundays

Well that's not my primary concern. Of chief concern is how the script really blows up her "improvements" yet dances around the word "cure" because I don't think hers has been cured.
Now by now you might be saying, "Well, who cares if she hasn't been cured? This sounds pretty good!" I mean, I get that, but if this is the best testimony they can put out, what does the average one look like?

 

[AfroSnowman]

Well that's not my primary concern. Of chief concern is how the script really blows up her "improvements" yet dances around the word "cure" because I don't think hers has been cured.
Now by now you might be saying, "Well, who cares if she hasn't been cured? This sounds pretty good!" I mean, I get that, but if this is the best testimony they can put out, what does the average one look like?

Well and for that matter it was for acute tinnitus right? <6 months. I mean from what I understand it is not unheard of for people to get better on their own, so an anecdote in its own right is pretty worthless. If the data was good that would be a different thing, but I thought that this was already a failed drug and discarded to the dustbin of our shattered hopes.

 

[RichardGuy]

If the data was good that would be a different thing, but I thought that this was already a failed drug and discarded to the dustbin of our shattered hopes.

That was my impression too. Didn't AM-101 fail spectacularly 3 years ago?

 

[ajc]

That was my impression too. Didn't AM-101 fail spectacularly 3 years ago?

It did.

Thomas Meyer, CEO of Auris Medical, is hopelessly flogging a dead horse. His own fortune is invested in this. He is trying to change the outcome measures so that the drug could enter the market, but I doubt it ever will. It already failed at THREE Phase 3 trial attempts, a fourth one isn't going to save it.

They also moved their headquarters to Bermuda recently from Switzerland. Why? Because operating from Switzerland was no longer possible due to the trainwreck that Auris Medical is.

DO NOT invest your hopes in their drugs.

 

[JohnAdams]

It is obviously a marketing video, but with a very hopeful claim we all long for.

I'll try it, shit.... 3 injections is nothing.

In February 2017, the U.S. Food and Drug Administration granted AM-111 Fast Track status.

https://www.biospace.com/article/auris-medical-fails-again-in-phase-iii-trial/

OK, let's do this for every fuggin tinnitus/hearing drug please.

 

[Striveon]

It says AM-101 failed? Can we still try it out or something?

 

[ChrisBoyMonkey]

Well and for that matter it was for acute tinnitus right? <6 months. I mean from what I understand it is not unheard of for people to get better on their own, so an anecdote in its own right is pretty worthless. If the data was good that would be a different thing, but I thought that this was already a failed drug and discarded to the dustbin of our shattered hopes.

Yes it failed but they believe the parameters were just set up a bad way (trial participants were to do TFI daily but it doesn't seem like they were). The FDA is actually helping them set up the next trial.

 

[JohnAdams]

How can they sell Ring Relief or any of this other shit like what Ryan Shelton is pushing with the Tonaki Tinnitus Protocol that is obvious bullshit but we can't just try this shit right now? I'm confused.

 

[Paulmanlike]

It did.

Thomas Meyer, CEO of Auris Medical, is hopelessly flogging a dead horse. His own fortune is invested in this. He is trying to change the outcome measures so that the drug could enter the market, but I doubt it ever will. It already failed at THREE Phase 3 trial attempts, a fourth one isn't going to save it.

They also moved their headquarters to Bermuda recently from Switzerland. Why? Because operating from Switzerland was no longer possible due to the trainwreck that Auris Medical is.

DO NOT invest your hopes in their drugs.

The real problem they had was 'proving' it worked - something that is extremely difficult to do with tinnitus subjects.