Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus

[attheedgeofscience]

I hope that they will find some kind of subgroup in their data that actually were helped by the drug but I am also a bit surprised that they could draw these kind of conclusions based on 58 people, which is only about one third of what they planed on. Would another 100 have changed the outcome? Is it possible that they are on the right track regarding what to target but their drug just didn't work well enough?

We have to assume that the data review was done very thoroughly by highly competent scientists.

But... reality influences science regardless of intelligence, and, if the patient intake had been more massive early on, then I, too, cannot help but play the mind game of "would that have changed anything"?

58 patients is indeed not much, and, with a heterogeneous condition such as tinnitus, even for a standardized patient population, then perhaps a larger sample would have changed the outcome (the AM-101 phase-II trial also only detected efficacy in a small sub-group of patients). But we have to remember the involvement of the GAP detection model used in pre-clinical studies, and, it is possible that the signs of tinnitus reduction (from those studies) in fact were "something" else (than what was being measured).

We have to trust that the investigators of Autifony know what they are doing, regardless of my above speculation.

 

[lapidus]

And this is exactly why I tried to calm people down and for some people I even said that stop bashing about Autifony being the saviour...

As much as I agree with you I have to say that it's quite easy to understand why people on here had so much hope though. We had 4 trialees on here. 2 of them had no effects while the other 2 had success. Those 2 might also have had the placebo so that would've made autifony working 100% from the trialees we had here. And the false hope got a lot bigger when Corrine's trial experience was posted under "success stories". People also had success with Trobalt, which made people think that AUT00063 would work even better.

Anyway, since 2 of 4 people on here had success, I'm still interested in seeing what conclusions Autifony will come to in their report.

 

[hoper]

AUT00063 doesn't work.
It's hopeless...

 

[attheedgeofscience]

Message From Autifony Therapeutics

A bit more official feedback directly from Autifony Therapeutics (for those who are interested). I received it today at lunch-time:

Thank you for your enquiry regarding Autifony's clinical trial in Tinnitus subjects, QUIET-1. As you will see from the recently issued statement {attached}, the trial discontinued enrolling in October 2015 following a planned interim analysis, which indicated that although safe and well tolerated, the trial was unlikely to meet its pre-specified endpoint for efficacy.

Naturally all staff and colleagues involved in the trial were disappointed with this result, but it is not unusual in early stage clinical trials of novel drugs. Furthermore, the drug continues in a study in patients with age-related hearing loss called CLARITY. If you require advice on Tinnitus or Hearing loss please contact your primary care physician (GP) in the first instance. More information on both conditions can be found by following these links;

http://autifony.com/autifony-tinnitus-phase-IIa-trial.asp

http://autifony.com/autifony-hearing-age.asp

Thank you for your enquiry.

 

[Lawrence Glickman]

Its clear that some treatments will work for some people and not others so the failure of a dramatic single treatment should be expected. Tinnitus is a description of symptoms not a single condition. Forget that fact and you will never get better. Most Doctors are too busy or ignorant to do a complete workup which would include your age, when you started to have the condition and are quick to go for an audio test as the be all and end all of the diagnosis. My ear damage for example occurred when I was 25-30 from rock music and my T started at 65. There is vast difference for me than someone who gets T immediately after an event such as the military patients. I have finally tracked down my causation to a parasitic infection and treating that has vastly reduced my problem. Be sure to go through a thorough workup looking for vascular problems , infection from parasites, viruses and bacteria before trying sound therapy etc. Best wishes to all.

 

[Silvio Sabo]

We have to assume that the data review was done very thoroughly by highly competent scientists.

But... reality influences science regardless of intelligence, and, if the patient intake had been more massive early on, then I, too, cannot help but play the mind game of "would that have changed anything"?

58 patients is indeed not much, and, with a heterogeneous condition such as tinnitus, even for a standardized patient population, then perhaps a larger sample would have changed the outcome (the AM-101 phase-II trial also only detected efficacy in a small sub-group of patients). But we have to remember the involvement of the GAP detection model used in pre-clinical studies, and, it is possible that the signs of tinnitus reduction (from those studies) in fact were "something" else (than what was being measured).

We have to trust that the investigators of Autifony know what they are doing, regardless of my above speculation.

I agree. We have to assume they are competent enough to do the work. It was just a me playing around in my own mind with a bit of skepticism.

I was one of those who thought they have been doing a good job and praised them for their tough inclusion criteria as this would have been a way to test the drug on a targeted subgroup of tinnitus patients. But now when we see the outcome I'm thinking that the field of tinnitus research has to get back to the basics. We have to build a solid test model. Perhaps a way to measure tinnitus objectively. Maybe with brain scans or something. Precisely how to do that I don't know or else I wouldn't be sitting here without millions of dollars in my bank account. But we have to exclude the human subjective aspect in the testings.

The next thing would be creating genetically altered animal models. Perhaps mice that express human genes coding for the ion channels. To screen for compounds one could do the same with simpler organisms such as worms (C. elegans that I have worked with is an exceptional model organism to work with).

There is a chance that Autifonys drug works on rats but not on humans. After all there are differences between humans and rats. And by that I mean more than appearance.

 

[SteveToHeal]

This is a sad day indeed. Everyone pinning their hopes on AUT.

 

[marqualler]

I don't have faith in the tinnitus community in being able to help itself (for reasons I have stated many many times re: poor lethargic commitment). I do a bit of behind the scenes work (with a focused goal), and besides that, things will just have to go the way they go I guess. I don't believe it is possible to revive the cause of Team Trobalt. The tinnitus community has failed itself so many times before that I have no confidence in the members ability to do, well, anything really! I will not start to engage my old contacts from the USA again. No way. Not happening. Sorry.

I agree 100% with everything ATEOS says in the post containing the above quote--but I don't necessarily agree with him that the cause of Team Trobalt is not possible to be revived, or even that Team Trobalt is "dead". It has evolved over time, sure, but knowing the "behind-the-scenes" work that both ATEOS is doing as well as @Markku and @Steve with pharmaceutical companies such as Autifony, or associations such as the British Tinnitus Association, the overall cause of Team Trobalt is still moving forward, even if the original group attempting to put legitimate scientific information about Trobalt is dormant.

How do we change this, then? WE NEED TO BE SERIOUS ABOUT RESEARCH. I also have been frustrated at the lack of "action" here--and I know that this is all in good intentions with many members--but I see over & over again posts about how disappointing it is that there isn't a drug on the market, why doesn't anybody care about tinnitus, etc., but not engaging in the "real" scientific knowledge. To be fair, what I have learned is there are politics and power dynamics involved in this work and they take careful handling to maintain (which kinda sucks a lot--in fact, and I'm soap boxing here--the very fact that the "system" in place to handle research is mostly based on capitalism has likely set back research on tinnitus and thousands of other medical afflictions by many years; I mean, it is a damn tragedy that hopeful avenues like stem cell research are all but forbidden in the USA because of political agendas; research should be massively government-funded...OK done soap boxing now).

I won't lie--this is a tough blow for me, and I'm sure it is for all of us here.

I'm an eternal optimist myself though and, knowing what I know about the work done behind-the-scenes, I still think research is headed in the right direction.

But WE NEED TO COME TOGETHER!

 

[Zechariah]

As much as I agree with you I have to say that it's quite easy to understand why people on here had so much hope though. We had 4 trialees on here. 2 of them had no effects while the other 2 had success. Those 2 might also have had the placebo so that would've made autifony working 100% from the trialees we had here. And the false hope got a lot bigger when Corrine's trial experience was posted under "success stories". People also had success with Trobalt, which made people think that AUT00063 would work even better.

Anyway, since 2 of 4 people on here had success, I'm still interested in seeing what conclusions Autifony will come to in their report.

Yes, it is easy to understand why people thought what they thought. Especially the people who like to use verbs like "hope" and "believe" when they discuss about scientific matters. Don't get me wrong but your message is a good example why people got so hyped (wishful thinking, false conclusions etc.)

I couldn't agree more with ATEOS:

"I cannot even begin to express my dissatisfaction with the incredible amount of clinical misinformation that floats around on a forum such as TinnitusTalk. Lots of arm-chair critics, wannabe experts, and self-proclaimed heroes who want to share their infinite wisdom of tinnitus."

But anyway, AUT00063 failing wasn't a big hit for me personally. I've been betting my chips on AM-101 which actually has some proven positive results - Although I've been told that my thoughts about "ear tinnitus" are so 90's and not valid anymore. My mild results with Trobalt actually suggests that my T could be still "an ear thing" but this may be a false assumption

And btw @attheedgeofscience and @marqualler , I assume that you have figured this out already but what comes to peoples activity to spread knowledge and push the like button in facebook - I assume they don't because it isn't going to help them personally (or atleast not right now). I guess it's the same shortsighted and self centered thing with voting - "My vote doesn't matter or change my life to better".

 

[marqualler]

And btw @attheedgeofscience and @marqualler , I assume that you have figured this out already but what comes to peoples activity to spread knowledge and push the like button in facebook - I assume they don't because it isn't going to help them personally (or atleast not right now). I guess it's the same shortsighted and self centered thing with voting - "My vote doesn't matter or change my life to better".

I hadn't thought of it that way before but yes I think that's a great way to think of it.

 

[Silvio Sabo]

I agree 100% with everything ATEOS says in the post containing the above quote--but I don't necessarily agree with him that the cause of Team Trobalt is not possible to be revived, or even that Team Trobalt is "dead". It has evolved over time, sure, but knowing the "behind-the-scenes" work that both ATEOS is doing as well as @Markku and @Steve with pharmaceutical companies such as Autifony, or associations such as the British Tinnitus Association, the overall cause of Team Trobalt is still moving forward, even if the original group attempting to put legitimate scientific information about Trobalt is dormant.

How do we change this, then? WE NEED TO BE SERIOUS ABOUT RESEARCH. I also have been frustrated at the lack of "action" here--and I know that this is all in good intentions with many members--but I see over & over again posts about how disappointing it is that there isn't a drug on the market, why doesn't anybody care about tinnitus, etc., but not engaging in the "real" scientific knowledge. To be fair, what I have learned is there are politics and power dynamics involved in this work and they take careful handling to maintain (which kinda sucks a lot--in fact, and I'm soap boxing here--the very fact that the "system" in place to handle research is mostly based on capitalism has likely set back research on tinnitus and thousands of other medical afflictions by many years; I mean, it is a damn tragedy that hopeful avenues like stem cell research are all but forbidden in the USA because of political agendas; research should be massively government-funded...OK done soap boxing now).

I won't lie--this is a tough blow for me, and I'm sure it is for all of us here.

I'm an eternal optimist myself though and, knowing what I know about the work done behind-the-scenes, I still think research is headed in the right direction.

But WE NEED TO COME TOGETHER!

The reason to why stem cell research is forbidden in the USA spells: Religion, Republicans, George W. Bush!

In Sweden a lot of ground research is funded by the government. Unfortunately tinnitus isn't a prioritized field. We do have researchers studying hearing disorders and among those tinnitus at the Karolinska Institute of Medicine but It's not huge.

 

[amandine]

In Sweden a lot of ground research is funded by the government.

I was under the impression that the Swedish government does not fund clinical trials whatsoever - am I wrong?

 

[marqualler]

The reason to why stem cell research is forbidden in the USA spells: Religion, Republicans, George W. Bush!

I'd say the third one is replaced by "all the GOP presidential candidates in 2016" but yes I agree. (Back to the No Politics rule now though, haha...)

 

[attheedgeofscience]

@valeri since you are the author of the very original thread on the petition to the ATA...

www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896

...I will make not, you per se, but the tinnitus community the following deal:

If the FB-post by [USERGROUP=11]@Team Trobalt[/USERGROUP] shown here...



...can achieve 1,000 rates/shares (in total, combined) AND the download link on the researchgate website can achieve 3,000 "reads"...

http://www.researchgate.net/publica...channel_openers_in_cultured_neuronal_networks

...then I am willing to join efforts to try to turn those figures into:

• 2k ratings on Facebook
• 5k reads on Researchgate

And... if that can be achieved, then I am willing to contact the researchers in the USA, and, ask them for their support and what we can achieve together.

But the tinnitus community has do its part, and how it does that is not up to me, but as always there needs to be some kind of virality involved e.g.

• spread the cause via PMs = 1 person contacts 3 others, asking them to do the same,
• spread awareness via internal alerts or the like,
• use sponsored ads (but don't ask the staff of TT to donate the money - they have already donated plenty)

Be creative!

attheedgeofscience
13/OCT/2015.

 

[Silvio Sabo]

I'd say the third one is replaced by "all the GOP presidential candidates in 2016" but yes I agree. (Back to the No Politics rule now though, haha...)

Yes and the reason for that is that a presidential candidate who would go to an election with the attitude of allowing stem cell research would be slammed by about 60 % of the religious christian population (read: insane religious morons).

 

[Peter61]

The problem is that research and development of a T cure is too diversified. In one country they are working on hair cell regeneration, in another country it's a drug that deactivates the hyperactive part of the brain where the T sound comes from, in another country it's autifony etc. etc. They should unite internationally and focus on ONE field of research at a time. I would say develop a drug that works on the brain (like there are so many drugs that work on the brain) and get all the scientists' noses in one direction. I bet there would be a drug within the next 3 years.

 

[Silvio Sabo]

The problem is that research and development of a T cure is too diversified. In one country they are working on hair cell regeneration, in another country it's a drug that deactivates the hyperactive part of the brain where the T sound comes from, in another country it's autifony etc. etc. They should unite internationally and focus on ONE field of research at a time. I would say develop a drug that works on the brain (like there are so many drugs that work on the brain) and get all the scientists' noses in one direction. I bet there would be a drug within the next 3 years.

One might think so but it just doesn't work that way. One thing is interests of the researchers. It would be hard to force someone to be creative in a field they have no or little interest in.

I agree that it's slowing things down, maybe. But how would we decide which field to start with? How would we prioritize? And who is supposed to make that call?

 

[preslys]

I'm sorry for this failure, that makes me hurt, believe me when I took my first dose of Trobalt I thought that autifony will succeed, especially that night of October 7 th 2015 when I woke up at 2:00 'I heard only absolute silence in my room.but it does not matter there's other treatment that are coming in the near future .don't lost hope it's not the end of the world. I have to thank @Markku for his great support and all his team also @attheedgeofscience for his efforts and others @Zimichael @nills @Viking @lapidus @amandine ...

And also my friends on "France acouphene" let me say them in french "merci beaucoup mes amis je vous souhait une totale guérison".

 

[attheedgeofscience]

And btw @attheedgeofscience and @marqualler , I assume that you have figured this out already but what comes to peoples activity to spread knowledge and push the like button in facebook - I assume they don't because it isn't going to help them personally (or atleast not right now). I guess it's the same shortsighted and self centered thing with voting - "My vote doesn't matter or change my life to better".

I know what you mean, but... one of the BIG advantages with Trobalt is that it is a drug that is already on the market. So the potential timeline for proving efficacy is much less (or assumed to be at least). Much more knowledge is necessary on Kv-channel openers when it comes to neurological conditions such as tinnitus. Remember... no one has done a study involving humans before. All we have to go on are those pre-clinical animal studies and in vitro pharmacodynamic analyses.

That's why a study on Trobalt (in humans) is both interesting and important (and may help patients in the short run also). Right now, the hurdle that any patient faces is that the medication is off-label (for tinnitus) and it is also not known how effective it is, nor how long treatment duration should go on for, nor is anything known in terms of treatment outcome in relation to chronicity of tinnitus. And many more questions. If these questions could be answered that would be huge step forward for the patient population and the prescribing physician (who right now has nothing to go on).

attheedgeofscience
13/OCT/2015.

 

[tomytl]

It's sad indeed, but this shows how science is based on facts and not (mostly not) on
some diffuse outcomes. Autifony made now a clear statement.

Let's see what's up next. Even the dissapointment is big, I'm thankful for all research
is done and for all the inputs here in this great forum.

 

[hoper]

so what's next?
nothing.

 

[Nucleo]

so what's next?
nothing.

SF34. But this one is far away still.

 

[amandine]

since you are the author of the very original thread on the petition to the ATA...

www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896

...I will make not, you per se, but the tinnitus community the following deal:

If the FB-post by @Team Trobalt shown here...



...can achieve 1,000 rates/shares (in total, combined) AND the download link on the researchgate website can achieve 3,000 "reads"...

http://www.researchgate.net/publica...channel_openers_in_cultured_neuronal_networks

...then I am willing to join efforts to try to turn those figures into:

• 2k ratings on Facebook
• 5k reads on Researchgate

And... if that can be achieved, then I am willing to contact the researchers in the USA, and, ask them for their support and what we can achieve together.

But the tinnitus community has do its part, and how it does that is not up to me, but as always there needs to be some kind of virality involved e.g.

• spread the cause via PMs = 1 person contacts 3 others, asking them to do the same,
• spread awareness via internal alerts or the like,
• use sponsored ads (but don't ask the staff of TT to donate the money - they have already donated plenty)

Be creative!

attheedgeofscience
13/OCT/2015.

I am repeating this so it doesnt get lost and forgotten in the thread - this is very important people so please can we do what ATEOS suggests and at the very least go to the fb page - dont post - click and share!! Sorry ATEOS for repeating this but I think it needs to keep getting highlighted so it doesnt disappear...thanks!

 

[hoper]

it's time to give up
in the next 30 years there is no drug on the way to help us...

 

[Dave111]

SF34. But this one is far away still.

2 years behind on AUT did i see somewhere.

 

[Steve]

it's time to give up
in the next 30 years there is no drug on the way to help us...

You really need to read the forum - the same goes for everyone who is giving up hope.

There are so many things that have helped people, so many options that may benefit you, just look at all of the success stories here. Even if the trials had been a roaring success they would not have had a 100% success rate. Look at other medical conditions and the necessary myriad approaches to treatment.

I'm still alive after 12 years of this, I hear mine virtually all of the time, I'm going through a nasty spike right now. I'm rubbish enough that I haven't devoted enough time to properly trying much in the way of treatment strategies but I cope and I even manage to enjoy myself like so many others in my position. You don't need a miracle cure to get back to living your life again, relying on one is a barrier to improving.

 

[monacco]

@amandine a lot of people have this ringing in ears but they don't know that it calls tinnitus.

 

[steinamo]

Lots of defeatist attitudes around here. I know it's shitty news, but you need to approach your condition with some positivity and hopefulness or I'd wager you'll only make it worse. There's still research being conducted elsewhere. Eventually, even if it's years from now, someone somewhere will come up with something that will help.

 

[amandine]

There's still research being conducted elsewhere.

Exactly there is research going on that we dont know about and will never know about cos the biotech company or the scientist will not get funding and the idea will never be trialed....the only reason we know about autifony is cos they secured the funding. So raising the funding is the key and there are ways to do this.....

 

[111]

Quite ironic that only in July 2015 they received and extra 8 million in funding, taking it to 23.5 million in total for series A.

Charles large made this comment about receiving the funding only in July 2015 -

"We are delighted that all Autifony's investors are supporting us with additional funding to build on the excellent progress that has been made to date in our hearing and schizophrenia programmes. We look forward to taking these programmes forward and to investigating further exciting opportunities."

Then just over 12 weeks later they pull the pin on the 063 trial, so much for excellent progress !

So what are they going to now invest that cash in, they say the following

Exploration of AUT00063 in a pilot study in patients with a cochlear implant

and

The clinical development of a second, differentiated Kv3 modulator, AUT00206, for the treatment of schizophrenia. AUT00206 is due to enter Phase I clinical trials later this year.

I suspect they will now concentrate on their schizophrenia programme to try to get some credibility back into the company for the investors