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

[attheedgeofscience]

My understanding is that all teams are non active at the moment.

OK. You are probably better informed than I am. But you could still be added to the sections, and, hence converse freely without anyone "watching" the brainstorming.

 

[attheedgeofscience]

My understanding is that all teams are non active at the moment.

Best chance in my opinion is a sponsored Facebook campaign - which - admittedly requires you to come up with cash. But it is very effective. Today, despite 2,000 views of this thread, the ratings have only gone up by about 20 in total. So... it's going to be a long stretch without some focused initiatives in order to reach 1k ratings. And sponsored posts are very effective. How to raise money is another matter...

Best of luck to those who wish to contribute.

 

[Sailboardman]

As William Shatner so wisely stated, many years ago: "Most likely the last thing I will hear in my life, will be my Tinnitus."

Hopers, keep on hoping, as you suffer and wait for a cure. Realist, listen to Shatner and accept your fate.

 

[another sean]

Well, I feel sad for everyone...Hopefully SF proves to be a better drug.

Whats SF?

 

[valeri]

What's a sponsored post?
@attheedgeofscience

 

[Markku]

What's a sponsored post?
@attheedgeofscience

It's paid advertising.

You can get any update in front of tons of faces.

However, the most success we've had with it was for the below Sounds of Tinnitus video, which ended up with the following stats:
21,797 views / 296 likes / 444 shares (as of October 14th, 2015)

It's extraordinary that it received more shares than likes. I don't think any other of our update has been like that.

Overall we put maybe $400-500 to advertising it, although during the campaign there were a few other updates we advertised as well. But the majority went for the video.

Now this isn't reproducible for a "hard" update like Prof. Moore. People simply won't like & share it as much (at the same rate). I can guarantee that. At least not as it is currently, it's too "dry and heavy" for the Facebook atmosphere, in my humble opinion.

Sure, with lots of money, it would be possible to generate the 1,000 likes and shares combined for the Prof. Moore update as it is, but my estimation is that at least over $1,000 would be needed, maybe more.

Videos / pictures do generally better. People like watching them.

But none of this is something that should be planned in this thread. This is no longer related to Autifony.

Like @attheedgeofscience recommended, you should join Team Awareness and we can go from there. I've added you to the group now. You can start a thread in the private forum.

 

[dan]

As William Shatner so wisely stated, many years ago: "Most likely the last thing I will hear in my life, will be my Tinnitus."

Hopers, keep on hoping, as you suffer and wait for a cure. Realist, listen to Shatner and accept your fate.

So you're going to accept your fate yes?

 

[OnceUponaTime]

What @attheedgeofscience has to offer is invaluable!
He did more for this community than ATA and BTA together so TT members time to get off your asses and help!

Done! Shared and all.

 

[swc5150]

My father just survived two forms of cancer that could not have been treated 10 years ago. I won't accept this fate

 

[Sailboardman]

@dan,

I'm accepting reality. Fate is just along for the ride. };-)

 

[dan]

@dan,

I'm accepting reality. Fate is just along for the ride. };-)

And what is your reality at the moment and for the foreseeable future?

 

[Sailboardman]

@dan,

I believe that T is so complex and evasive, that we haven't even scratched the surface, of truly understanting how to treat it with drugs. I think Autifony's galant attempt at trying to find a valid treatment, but ultimately failing it's mission, certifies this.

I also believe, we will not see a "cure," for many decades to come. A "real" treatment to silence T in all sufferers, maybe in 20-30 years?

Martin69, read somewhere, there are around 400 ways, someone can acquire T. If this is even half right, how much research and testing will it take to create a drug, to treat a condtion, with that many variables and permutations?

This is on par with finding a cure for cancer, MS or similar complicated maladies. It ain't gonna be right around the corner.

In previous posts, I questioned what if Autifony's drug is a bust? Where do we go from here? Well, we are at that crossroad now and let's see how long we'll have to wait, to be baited by more promises of treatments and cures.

My opinions of course.

 

[JohnnyMx]

@Sailboardman

Man, if all mankind had your way of seeing life, we yet would travel long distances on horseback, and we would had not even discovered penicillin. For our wellness, there are many people who do not surrender to seek an answer, these people change the world, and maybe one of them will find a cure for T.

Regards.

 

[valeri]

Since the discovery of penicillin there hasn't been anything so revolutionary!
And it's been nearly 90 years!
So all in all its a grim reality that modern medicine is simply just modern in terms of fancy gadgets and equipment!
Curing something, unless you need parts taken out, is very far from success story!

 

[Roger Wolf]

Since the discovery of penicillin there hasn't been anything so revolutionary!
And it's been nearly 90 years!
So all in all its a grim reality that modern medicine is simply just modern in terms of fancy gadgets and equipment!
Curing something, unless you need parts taken out, is very far from success story!

Because there wasn't really any need for it lol.
We're only now beginning to understand how the inner ear truly works. Perhaps not enough to get a cure. But we're damn close.

 

[PhilB]

I have spoken with a number of people within the research community throughout the last two days. It's been very intense. The consensus seems to be that for the QUIET-1 trial to have been terminated based on interim data, it must mean that there has been very little efficacy shown. My own opinion regarding sample size (i.e. N = 58) being too small is also reflected by the opinions of those I have been in touch with.

The findings will be published in due course, therefore any speculation is essentially futile but I can't help wondering if the failure to obtain positive results may be at least partly due to false positives in the control group. For example (and this is just hypothetical), let us suppose that of the 58 people the sample, 29 were given AUT63 and 29 were given the placebo. Of the 29 given AUT63, let us suppose that 15 reported improvement and 14 reported no change. That might sound like proof of efficacy, right? But what about the control group? It cannot be assumed that the 29 people in the control group would all report no change. It is quite possible that of the 29 in the control group, 15 would report improvement and 14 would report no change. In that scenario, there would be no difference between the outcomes of the control group and the AUT63 group, therefore no proof of efficacy. So why would the people in the control group (who are taking sugar pills or something similar) report improvement in their T? We need to remember that the control group are all T sufferers who are eager for something that will alleviate their condition. Quite a few of them are likely to convince themselves that the sugar pills are making a difference. I don't have access to any information other that which is contained in Autifony's statement but I am just trying to illustrate the difficulty in obtaining proof of efficacy from such a small sample, particularly when dealing with a condition which is essentially subjective and cannot be empirically measured.

 

[Drecul]

The findings will be published in due course, therefore any speculation is essentially futile but I can't help wondering if the failure to obtain positive results may be at least partly due to false positives in the control group. For example (and this is just hypothetical), let us suppose that of the 58 people the sample, 29 were given AUT63 and 29 were given the placebo. Of the 29 given AUT63, let us suppose that 15 reported improvement and 14 reported no change. That might sound like proof of efficacy, right? But what about the control group? It cannot be assumed that the 29 people in the control group would all report no change. It is quite possible that of the 29 in the control group, 15 would report improvement and 14 would report no change. In that scenario, there would be no difference between the outcomes of the control group and the AUT63 group, therefore no proof of efficacy. So why would the people in the control group (who are taking sugar pills or something similar) report improvement in their T? We need to remember that the control group are all T sufferers who are eager for something that will alleviate their condition. Quite a few of them are likely to convince themselves that the sugar pills are making a difference. I don't have access to any information other that which is contained in Autifony's statement but I am just trying to illustrate the difficulty in obtaining proof of efficacy from such a small sample, particularly when dealing with a condition which is essentially subjective and cannot be empirically measured.

Still the placebo effect is well known in trails with new medicine for that reason they often switch the control group after a period of time. Given the fact that T is so diverse amongst people both in outcome and cause one would expect a large trail group (at least larger than merely 58 people). To me even more odd is the lenght of the trail and the dosage. (As I understood only a single dosage in testing). Here is a company that spend quite some time and money to develop a medicine, trowing in the towel after such a small trail group/period.

That to me is unprecedented.

 

[Guest57247683]

Somehow I get the feeling that there is something going on behind the scenes with this drug development and research... I truly don´t know but seems strange to just let to go all the good work so far. Hopefully something BIG and positive will come out of it.

 

[derpytia]

I'm trying to find the post ATEOS mentioned on FB but I can't seem to find it???

 

[amandine]

I'm trying to find the post ATEOS mentioned on FB but I can't seem to find it???

Don't forget to read the professors literature as he is counting the reads on that too.....plus like and share the fb post

Since the discovery of penicillin there hasn't been anything so revolutionary!

Not true Valerie! Face transplants, womb transplants, hand transplants, paralysed man walks using his thoughts only, ebola sorted......

So why would the people in the control group (who are taking sugar pills or something similar) report improvement in their T? We need to remember that the control group are all T sufferers who are eager for something that will alleviate their condition. Quite a few of them are likely to convince themselves that the sugar pills are making a difference.

One of our very own members here said that he felt that the biggest improvement he had in his T was down to the Autifony drug and he had tried am 101 and trobalt as well before autifony and in fact did not continue with the injections of am 101 so he could participate in autifony.
Was all this placebo? And Lady D - was she placebo?

 

[Silvio Sabo]

Since the discovery of penicillin there hasn't been anything so revolutionary!
And it's been nearly 90 years!
So all in all its a grim reality that modern medicine is simply just modern in terms of fancy gadgets and equipment!
Curing something, unless you need parts taken out, is very far from success story!

Just like @amandine already said. This is just not true. In fact there has been so much development it's insane! The thing is that just like in every other field the medical field has come such a long way that it's hard to come up with something super revolutionary like inventing the wheel. We know at least a little about everything so taking one huge leap in just one step is hard to do nowadays.

But things like medication for blood pressure has changed so many lives. People are no longer dying in their 40's because of hypertension like they used to. Then we have medication for people who have ulcers like Losec that has changed lives (my Mother being one of them).

If you go into surgery there has been a tremendous amount of advancement. I can just take example of my Father that tore his meniscus some 30 years ago and that was it for his football career. Now you have a surgery with local anesthesia and walk out of the hospital the same day and can start rehabilitation in about a week and are back on the field in about 3-4 weeks. If we stick to knees there are ligament injuries like torn ACLs that they just couldn't fix 30 years ago. Now you're back in about 6-8 months. And not to mention transplantation of organs. We can transplant just about everything but the brain and parts of the CNS. We couldn't do that some 10-20 years ago. Not to the same extent at least.

A friend of mine has a daughter that was born prematurely. I don't remember which week but somewhere around week 25-26 I think. That's pretty early. She had to be incubated for nearly two months. However the survival rate for babies born so early today is whopping 95 %! just 10-15 years ago it was only 5-10 %! That is an astronomical advancement in short period of time!

The thing is we can actually grow new organs or whole body parts that are genetically identical to the patient. We can take their blood and clone a whole new body if we wanted to. At least technically. What is stopping us is Religion and moral aspects. F.i. stem cell research is pretty much banned in the USA because of political and religious reasons. We have GMO that is being targeted for the same reasons. Ignorance and religion! We can save millions of children in the third world by growing Golden Rice (GMO rice that produces vitamin A) but it's not being done because of above mentioned reasons.

 

[linearb]

Guys, this is in one way is a big step, it has shown the pharma model up for the imposter that it really is. Essentially bathing the brain in chemicals is an old capitalist model for disease, money first and patient second, now its looking like cellular repair is back on the cards, of course there is no business model for this, but with the ever growing incompetence within otolaryngology/otology in dealing with hearing disorders. I am sure someone will come in to fill the gap. With mutebutton falling and now this: roll on the failure of pharma as we shift to cell based therapy.

If anything I think the Autifony story shows the difficulties of drug development, but also points towards a bright future for pharmaceuticals. Being able to make and test molecular target drugs based on 3d computer models of ligands is very new. Being wrong about a specific Kv subchannel is no problem; other subchannels can be targeted through the same means.

 

[Aaron123]

The findings will be published in due course, therefore any speculation is essentially futile but I can't help wondering if the failure to obtain positive results may be at least partly due to false positives in the control group. For example (and this is just hypothetical), let us suppose that of the 58 people the sample, 29 were given AUT63 and 29 were given the placebo. Of the 29 given AUT63, let us suppose that 15 reported improvement and 14 reported no change. That might sound like proof of efficacy, right? But what about the control group? It cannot be assumed that the 29 people in the control group would all report no change. It is quite possible that of the 29 in the control group, 15 would report improvement and 14 would report no change. In that scenario, there would be no difference between the outcomes of the control group and the AUT63 group, therefore no proof of efficacy. So why would the people in the control group (who are taking sugar pills or something similar) report improvement in their T? We need to remember that the control group are all T sufferers who are eager for something that will alleviate their condition. Quite a few of them are likely to convince themselves that the sugar pills are making a difference. I don't have access to any information other that which is contained in Autifony's statement but I am just trying to illustrate the difficulty in obtaining proof of efficacy from such a small sample, particularly when dealing with a condition which is essentially subjective and cannot be empirically measured.

Assuming the participants were properly randomized, then the numbers you use demontrate no efficacy. A control group is used to show what would have been expected due to the placebo effect or other random characteristics not accounted for in the analysis. In principle, the only thing that should differ between the treatment and control group is the treatment itself. If half of the people in the control group respond due to the placebo effect then we would expect half in the treatment group to respond due to the placebo effect. It doesn't make any sense to say that half of the control group had a positive effect due to the placebo effect but that half of the treatment group had a genuinely positive effect. After all the people in the treatment group are also "T sufferers who are eager for something to alleviate their condition" so they have the same incentive to respond due to the placebo effect.

I do agree about the challenges raised by the small sample size. It increases the likelihood that a few "bad" draws can affect the outcome. In particular, in the case of tinnitus even with the exclusion criteria we know there many, many characteristics that are not accounted for in the inclusion/exclusion criteria or the analysis. Those should be evenly distributed across the treatment and control samples due to randomization. This should be true regardless of whether the sample is large or small However, with small samples, there is a greater likelihood of running into problems.

Suppose there is something that isn't accounted for in the inclusion criteria or randomization but that makes it more likely that you won't respond to treatment. Randomization should ensure that people with this characteristic are evenly distributed in the treatment and control groups. If we have a large sample, this is almost certainly true. If we have a small sample, there is a higher probability that we could be unlucky and have most of those people end up in the treatment group. If this happens it will be hard to find an effect. I'm not saying this happened in this case - just that there is a higher probability of something like this happening if the sample is small.

 

[Silvio Sabo]

Assuming the participants were properly randomized, then the numbers you use demontrate no efficacy. A control group is used to show what would have been expected due to the placebo effect or other random characteristics not accounted for in the analysis. In principle, the only thing that should differ between the treatment and control group is the treatment itself. If half of the people in the control group respond due to the placebo effect then we would expect half in the treatment group to respond due to the placebo effect. It doesn't make any sense to say that half of the control group had a positive effect due to the placebo effect but that half of the treatment group had a genuinely positive effect. After all the people in the treatment group are also "T sufferers who are eager for something to alleviate their condition" so they have the same incentive to respond due to the placebo effect.

I do agree about the challenges raised by the small sample size. It increases the likelihood that a few "bad" draws can affect the outcome. In particular, in the case of tinnitus even with the exclusion criteria we know there many, many characteristics that are not accounted for in the inclusion/exclusion criteria or the analysis. Those should be evenly distributed across the treatment and control samples due to randomization. This should be true regardless of whether the sample is large or small However, with small samples, there is a greater likelihood of running into problems.

Suppose there is something that isn't accounted for in the inclusion criteria or randomization but that makes it more likely that you won't respond to treatment. Randomization should ensure that people with this characteristic are evenly distributed in the treatment and control groups. If we have a large sample, this is almost certainly true. If we have a small sample, there is a higher probability that we could be unlucky and have most of those people end up in the treatment group. If this happens it will be hard to find an effect. I'm not saying this happened in this case - just that there is a higher probability of something like this happening if the sample is small.

Yeah it's basic statistics. I'm sure however that they are competent enough to crunch the numbers them selves. However I can't not to think the same so I'm anxious to see the report they are going to write when the final data has been analyzed.

Also out of the 58, half should have been on placebo so you actually only have 24 subjects that are on the drug. If I still remember my statistics it is possible to draw conclusions on such a small sample size depending on what kind of results you have (if you don't have a big spread). I think It's still possible to get low enough p-values.

Therefore I think the drug must have been a complete failure for them to be able to come to these conclusions. Simply put, Mrs. D was probably the only one with any real benefits of a larger magnitude.

 

[Sailboardman]

@JohnnyMx,

Well, it took a couple of thousand years to get from riding horseback to riding in motor vehicles or planes. However, I agree with your last sentence: "and maybe one of them will find a cure for T." The key word is maybe.

I assume you're younger than me and hopefully before you die, you'll be cured. I'm sincere about that.
I unfortunately, don't have that kind of time, to wait for maybe's.

 

[Drecul]

Don't underestimate the effect of a placebo. All effects in early trails could be due to the placebo effect for both a sugar pill and the real medicine. People have managed to cure themselves with placebo's Even side effects can be caused by placebo's (if you tell them) That's the suggestibility of the sub-conscious mind.

Placebo's can go a long way and I seriously doubt that 58 people and 28 days is sufficient to rule out a placebo effect.
If both groups did not have any effect within this marginal study, it would be the first trail where placebo effect did not played a role.

It does not make sense.

 

[linearb]

@JohnnyMx,

Well, it took a couple of thousand years to get from riding horseback to riding in motor vehicles or planes.

Sure, and it took us less than 100 years to go from extremely dangerous rudimentary aircraft, to safe and efficient vehicles as a matter of daily convenience.

Similarly, it took us a couple of thousand years to get from "make tea from these flowers to ease pain" to "these flowers contain a variety of specific molecules including morphine and codeine" -- and 100 years to go from isolating morphine, to being able to build it from the ground up with atomic components, map out the exact ligands it agonizes (and the DNA sequences which code for both the part of the plant that produces the drug, as well as the human protein which encodes the receptor).

So, things are speeding up. Whether or not this will translate to a widespread, effective tinnitus treatment in the next 10-20 years remains to be seen, but I don't think there's any reason to assume it's a pessimistic outlook. We clearly have a very incomplete understanding of tinnitus, but we understand an astonishing amount about how it works at a structural/mechanical level as compared to only 15-20 years ago. Likewise, custom drug synthesis is still a very new and evolving field.

 

[Silvio Sabo]

Don't underestimate the effect of a placebo. All effects in early trails could be due to the placebo effect for both a sugar pill and the real medicine. People have managed to cure themselves with placebo's Even side effects can be caused by placebo's (if you tell them) That's the suggestibility of the sub-conscious mind.

Placebo's can go a long way and I seriously doubt that 58 people and 28 days is sufficient to rule out a placebo effect.
If both groups did not have any effect within this marginal study, it would be the first trail where placebo effect did not played a role.

It does not make sense.

The thing with placebo is that it's very real and measurable. People don't just think they get better they in fact DO get better and can sometimes even be cured completely. And it doesn't mean that they just imagined their illness! They were in fact sick and did in fact get well with just a sugar pill. It's hard to grasp but it's the truth. It's fascinating really! And there is no real explanation to how or why this happens. It's a bit of a mystery.

Some people will in better on the drug. Even if it's not working = placebo effect! And if your drug is not better to the extent that you can prove it with statistical analysis you will end up with wath Autifony must have had.

The time frame should be irrelevant as you do a comparison between placebo and your drug. The only thing where time frame would be important is if it takes a long time for the drug to work. But in the pre-clinical tests and animal testing the drug worked rather quickly.

 

[Drecul]

The thing with placebo is that it's very real and measurable. People don't think they get better they in fact DO get better and can sometimes even be cured completely. And it doesn't mean that they just imagined their illness! They were in fact sick and did in fact get well with just a sugar pill.

The time frame should be irrelevant as you do a comparison with the drug. Because some people will in fact get better even on placebo as well as on the drug. Even if it's not working! And if your drug is not better to the extent that you can prove it with statistical analysis you will end up with wath Autifony must have had.

I agree however the same placebo effect can be seen in the subject that takes the medicine. What you are saying here is that the medicine group did not have any effect compared to the placebo, which would mean that there wasn't a placebo effect present amongst the people who took the real drug. That's simply not possible.

And again 58 people and 28 days is not sufficient to determine all this.

 

[Silvio Sabo]

I agree however the same placebo effect can be seen in the subject that takes the medicine. What you are saying here is that the medicine group did not have any effect compared to the placebo, which would mean that there wasn't a placebo effect present amongst the people who took the real drug. That's simply not possible.

And again 58 people and 28 days is not sufficient to determine all this.

No that is not what I said. You have placebo effect happening in both groups. However in the trial group you should be able to see results BETTER than the control group. And not just better in the fact that you say "oh we have a couple of more people that got better in the trial group". You have to prove this with statistical analysis. Or else you draw the conclusion that the drug is not working as it's not better than placebo. It's just equally good, or bad, depending on how you look at it.

This is why you must have a sample size of a certain size so that you can say that your - hopefully - better results must be because the drug is working and not because you happened to have a few more people in the trial group that had benefits due to placebo. Because you will have that in both groups!

58 people and 28 days could be enough. The drug worked rather quickly in prior trials and when tested in animal models. When you crunch the numbers you usually do a t-test where you get a p-value. If it's low enough (usually below 0,05) you can say that your results are statistically solid.

I too am skeptical, don't get me wrong. All I'm saying is that it is possible and I'm rather sure it must be so or else they wouldn't have pulled the plug.