AM-101 TACTT1 Results Released

[bill 112]

I got T back in 2011 from q-tips well at least thats what I think caused it which actually disappeared after a few months completely so I continued to live my life again I went to a club one night as my friend was performing at the club so I kinda had to go as this was his big break I even brought hearing protection just in case and guess what T came back and stayed so I habituated to it and got life back on track.I stayed away from clubs concerts etc.Then at the start of 2014 I was exposed to very high frequency sound and now things have gone crazy really bad T and H as a result but all my hearing tests are perfect which makes me wonder if this is an auditory nerve problem??Anyway what im getting at is would I be suitable for this treatment would this help me??Thanks

 

[JohnG]

Perhaps I am confused. (Believe me, it happens more than I care to admit!)

Anyway, I thought AM-101 is still in clinical trials. How exactly is it proven?

Stephen Nagler

Well, I guess I mean seems statistically significant from Phase II. So if we mean proven passing Phase III, then no. But if we mean so far the results look statistically significant, then yes.

Proven compared to HBOT which seems like more of a long shot from what I've read. Especially after a few weeks post trauma. Sorry, if I did not choose my lexicon correctly but I see a very significant statistical weight in my favour compared to HBOT. You may dispute that, but I have to take the course of action with the best possible probability and it is not HBOT.

 

[Dr. Nagler]

@JohnG -

Phase III is the phase that proves efficacy. As I see it, all other phases should be viewed as preliminary. You may choose to disagree, but then why subject any treatment to Phase III trials in the first place?

I find the assertion that AM-101 is somehow a "proven treatment" to be wishful thinking at best. It would be wonderful if the Phase III trials demonstrated efficacy, but until such time that they do - if they do - then nothing is proven.

Stephen Nagler

 

[JohnG]

@JohnG -

Phase III is the phase that proves efficacy. As I see it, all other phases should be viewed as preliminary. You may choose to disagree, but then why subject any treatment to Phase III trials in the first place?

I find the assertion that AM-101 is somehow a "proven treatment" to be wishful thinking at best. It would be wonderful if the Phase III trials demonstrated efficacy, but until such time that they do - if they do - then nothing is proven.

Stephen Nagler

I would respectfully disagree given the results so far. Yes, phase III is efficacy but phase II still has a therapeutic dose. It is good to be objective, but your statement: "Phase III trials demonstrated efficacy, but until such time that they do - if they do - then nothing is proven" is not quite accurate and completely disregards any data so far. So I would have to disagree with you but no matter. I'm getting help...and listening to statements like that would only put me into permanent disability. So say what you must, I disagree and I am moving forward.

 

[Dr. Nagler]

I would respectfully disagree given the results so far. Yes, phase III is efficacy but phase II still has a therapeutic dose. It is good to be objective, but your statement: "Phase III trials demonstrated efficacy, but until such time that they do - if they do - then nothing is proven" is not quite accurate and completely disregards any data so far. So I would have to disagree with you but no matter. I'm getting help...and listening to statements like that would only put me into permanent disability. So say what you must, I disagree and I am moving forward.

I am very glad you are moving forward, but please enlighten me. How can listening to something anybody posts on this site put you "into permanent disability?"

Stephen Nagler

 

[JohnG]

I am very glad you are moving forward, but please enlighten me. How can listening to something anybody posts on this site put you "into permanent disability?"

Stephen Nagler

Well, if I act on bad advice, like I did the past "doctors", then yes, I have a disabling health problem that was unnecessary and could have been prevented. From now on, I will use my own engineering acumen to analyse data and make my own health decisions. The best thing I did was fire my family doctor. I need to find medical professionals that I know are on the same treatment plan that I approve.

 

[JohnG]

• Improvement in TLQ from baseline to Day 90 of at least 50% was seen for 14% of patients in the placebo group compared with 42% of patients in the high-dose group
• At Day 90, the mean tinnitus loudness in the high-dose group was 43.2% lower than at baseline (49.5% for unilateral cases). This compares with an improvement of 17.7% (10.0%) for the placebo group.

Some excerpts from the link @JohnDoe posted. I was thinking about the fact that many people get better after the T onset. The trials showed the drug at the high does to be nearly twice as effective. So that was a good start, but by how much did T improve from the two groups. Over 42% in the high does group had improvements of at least 50%, so some had more. Compared to only 14% placebo. Average improvement of 43% to about 18% (drug vs placebo). That some great information, without a doubt this drug has an effect on T. Good luck to everyone entering the trials!

It seems pretty convincingly statistically significant so far. Better than I've seen from steroids or HBOT. Especially well after the trauma. From their website:

"The trial demonstrated a dose-dependent and persistent improvement in several patient reported outcomes (PROs). Patients suffering from unilateral tinnitus following acute acoustic trauma or otitis media who received AM-101 0.81 mg/mL showed a gradual and statistically significant improvement 90 days post-treatment in tinnitus loudness, annoyance, tinnitus-related sleep difficulties and in overall tinnitus impact (THI-12 questionnaire) compared with placebo. In the analysis of covariance (ANCOVA), p-values were <0.02 for these outcomes. At Day 90, the mean improvement in tinnitus loudness was 48% in the high-dose group, compared to 28% in the low-dose group and 9% in the placebo group. Overall, 64% of patients in the high-dose group rated their tinnitus severity at Day 90 compared with baseline as ''much improved'' or ''very much improved,'' compared with 44% and 35% of patients in the low-dose and placebo groups, respectively." ....but 248 patients. Still...

 

[Dr. Nagler]

Well, if I act on bad advice, like I did the past "doctors", then yes, I have a disabling health problem that was unnecessary and could have been prevented.

Either Treatment X works or it doesn't. What I or anybody else on this board might have to say about it cannot possibly change that in the least.

Stephen Nagler

 

[JohnG]

Either Treatment X works or it doesn't. What I or anybody else on this board might have to say about it cannot possibly change that in the least.

Stephen Nagler

Probably this thread needs to go under AM101 ..but anyway....I'll go with treatment X has a good opportunity: "The trial demonstrated a dose-dependent and persistent improvement in several patient reported outcomes (PROs). Patients suffering from unilateral tinnitus following acute acoustic trauma or otitis media who received AM-101 0.81 mg/mL showed a gradual and statistically significant improvement 90 days post-treatment in tinnitus loudness, annoyance, tinnitus-related sleep difficulties and in overall tinnitus impact (THI-12 questionnaire) compared with placebo. In the analysis of covariance (ANCOVA), p-values were <0.02 for these outcomes. At Day 90, the mean improvement in tinnitus loudness was 48% in the high-dose group, compared to 28% in the low-dose group and 9% in the placebo group. Overall, 64% of patients in the high-dose group rated their tinnitus severity at Day 90 compared with baseline as ''much improved'' or ''very much improved,'' compared with 44% and 35% of patients in the low-dose and placebo groups, respectively."

 

[Dr. Nagler]

So why bother with Phase III trials at all?

Click Here

And Here

Stephen Nagler

 

[jazz]

I'm really hoping AM-101 will also work for chronic tinnitus. But the drug probably won't hit the market until 2016 or perhaps later. The European Trial, which includes a post-acute section (up to 12 months), won't be concluded until 2015.

Who knows how long it'll take the FDA to approve it!

 

[cullenbohannon]

Dr.Nagler , I wasn't aware of this. Im curious how do you think they get passed the phase 2 testing. Do they lie about the results ( Which I suppose wouldn't be the first time a drug company did such a thing). I also have trouble understanding how an investment firm would invest so much money if they did not have evidence that it worked. I just hoped there would be more oversight for such things. I still have hopes that will pass stage three testing, im just not sure wether or not I will be participating. I was having doubts before this, and now I have more to think about. @JohnG I am as hopeful as you man, but I do think Dr.Nagler is doing his job. It would be incredibly irresponsible for a licensed doctor to endorse a treatment that hasn't been approved for treatment. But that doesn't mean you should not go through with the trials.

http://seekingalpha.com/article/256697-why-phase-3-trials-fail-what-investors-need-to-know

According to a McKinsey study analyzing phase 3 trial failures reported from 1990-2002, the results had numerous implications for pharma.Focusing on small-molecules (656 Phase 3 compounds), 58% were successful.This of course implies a 42% failure rate; a staggering sum given that both safety and efficacy should have already been demonstrated.The analysts were able to evaluate in depth 73 of the 212 failures. Shockingly, the results indicated that a full 50% of these compounds failed for a lack of efficacy compared to placebo!Another 30% were for safety concerns and the final 20% could not be proven safer or more effective than the drugs already on the market.Phase 2 is designed to establish efficacy in patients, and clearly there are shortcomings at this stage.The efficacy failures could be attributed to two main causes: mechanistic novelty and endpoint definition.Qualitative endpoints failed more often than defined endpoints.Interestingly, according to the study:

So why bother with Phase III trials at all?

Click Here

And Here

Stephen Nagler

 

[cullenbohannon]

@jchinnis curious as to what your thoughts are on the matter.

 

[JohnG]

So why bother with Phase III trials at all?

Click Here

And Here

Stephen Nagler

In medicine you have to do you due diligence to check and double check...then counter check. I appreciate Phase III; however, I don't have that luxury. If you were the devil (only for illustration don't take it personally) and came down and said, "John you will get T. I will only give you the time to choose it". Then of course, I would choose after phase III. Sadly, I didn't get the chance to choose when to get it.

So I will go with half the checking and double checking but I still feel the statistics are more favourable than other treatments for me at this juncture in time. Otherwise, I would be chiming in with you on safety first..better check and double check and super duper check that data again.

Also, there is risk to any medical procedure. This involves injection into the middle ear. You could get infection, deafness or even worse T. That is a risk even after phase III goes well.

 

[Dr. Nagler]

Just so we're all on the same page here.

I'm not saying that the drug (AM-101 in this case) doesn't work.

All I am saying is that in my opinion it has yet to be proven that it does. And (again in my opinion) it is misleading to suggest otherwise.

Is it worth it to give the drug a try anyway? That is a personal decision.

Stephen Nagler

 

[cullenbohannon]

I do get that, i just didn't know so many other phase 3 drugs fail.

Just so we're all on the same page here.

I'm not saying that the drug (AM-101 in this case) doesn't work.

All I am saying is that in my opinion it has yet to be proven that it does. And I think it is misleading to suggest otherwise (again, in my opinion).

Stephen Nagler

 

[JohnG]

Dr.Nagler , I wasn't aware of this. Im curious how do you think they get passed the phase 2 testing. Do they lie about the results ( Which I suppose wouldn't be the first time a drug company did such a thing). I also have trouble understanding how an investment firm would invest so much money if they did not have evidence that it worked. I just hoped there would be more oversight for such things. I still have hopes that will pass stage three testing, im just not sure wether or not I will be participating. I was having doubts before this, and now I have more to think about. @JohnG I am as hopeful as you man, but I do think Dr.Nagler is doing his job. It would be incredibly irresponsible for a licensed doctor to endorse a treatment that hasn't been approved for treatment. But that doesn't mean you should not go through with the trials.

http://seekingalpha.com/article/256697-why-phase-3-trials-fail-what-investors-need-to-know

According to a McKinsey study analyzing phase 3 trial failures reported from 1990-2002, the results had numerous implications for pharma.Focusing on small-molecules (656 Phase 3 compounds), 58% were successful.This of course implies a 42% failure rate; a staggering sum given that both safety and efficacy should have already been demonstrated.The analysts were able to evaluate in depth 73 of the 212 failures. Shockingly, the results indicated that a full 50% of these compounds failed for a lack of efficacy compared to placebo!Another 30% were for safety concerns and the final 20% could not be proven safer or more effective than the drugs already on the market.Phase 2 is designed to establish efficacy in patients, and clearly there are shortcomings at this stage.The efficacy failures could be attributed to two main causes: mechanistic novelty and endpoint definition.Qualitative endpoints failed more often than defined endpoints.Interestingly, according to the study:

Oh believe me, I was burnt on a drug that passed phase III and was on the market. Even phase III can be whitewashed, as you pointed out. Drug companies want to get their investment through the door and even many, if not most, doctors get most of their pharmaceutical knowledge from the drug pushers...I mean drug reps. Even a good phase III is dubious at best. In a perfect world, I would never take this risk...but here I am...with T. Now, I could not take any drug......and just hope for the best. Or, I could take a risk and have somewhat better odds.

 

[JohnG]

Just so we're all on the same page here.

I'm not saying that the drug (AM-101 in this case) doesn't work.

All I am saying is that in my opinion it has yet to be proven that it does. And (again in my opinion) it is misleading to suggest otherwise.

Is it worth it to give the drug a try anyway? That is a personal decision.

Stephen Nagler

OK...OK I redact the word proven....you win..happy. It is statistically favourable so far. Hope it makes you happy, if not...so sorry.

 

[Dr. Nagler]

John, my standard is the reliable and verifiable prospective double blind randomized prospective study published in a reputable juried scientific journal.

Even if the AM-101 Phase III trials were successful, they would not meet that standard (i.e., the results would not have been independently reproduced), but I would accept them anyway. I would not accept Phase II results as proof of efficacy under any circumstances.

But just to repeat -

Do I think it's worth it to give the drug a try anyway? That is a personal decision between you and your doctor.

Stephen Nagler

 

[Dr. Nagler]

OK...OK I redact the word proven....you win..happy. It is statistically favourable so far. Hope it makes you happy, if not...so sorry.

I'll be happy if the drug works. That's what will make me happy.

Stephen Nagler

 

[JohnG]

I'll be happy if the drug works. That's what will make me happy.

Stephen Nagler

Now we are on the same page!!!

 

[Hudson]

I'm really hoping AM-101 will also work for chronic tinnitus. But the drug probably won't hit the market until 2016 or perhaps later. The European Trial, which includes a post-acute section (up to 12 months), won't be concluded until 2015.

Who knows how long it'll take the FDA to approve it!

Six months at least, after submission of the total regulatory package. That's been my experience although I have dealt with the FDA on a different regulatory level than medical stuff.

 

[Hudson]

Six months at least, after submission of the total regulatory package. That's been my experience although I have dealt with the FDA on a different regulatory level than medical stuff.

We also have to keep in mind this: as much of a cinderella story as we'd like it to be, Auris is in this for the money at the end of the day. They will not hurry along their process for regulatory approvals in the various agencies to benefit those of us suffering. They're going to make sure every t is crossed, every i is dotted. The paperwork for a regulatory approval is mind boggling.

 

[jchinnis]

@jchinnis curious as to what your thoughts are on the matter.

I haven't followed this very closely, and my available time has shrunk for a little while.

The way I think about these things is in terms of the probability I give to a treatment working (to what degree, etc.) for a certain type of person. That probability does indeed rise with signs of efficacy from a Phase II trial.

A lot depends on the details of the Phase II trial. Things like exclusion criteria, endpoint definitions, attrition, measurement of subjective criteria, etc. are important.

When thinking about the probability AM-101 will work for you, you need to keep the base rate in mind, too. Most Phase III trials are failures. So you need some better than typical signs from the Phase II trial (or elsewhere) that AM-101 will work for you.

Isn't this topic on HBO therapy? Where are the Phase III randomized trials on that for tinnitus? Looks like it would be really simple to do.

 

[Littlebailey]

Hey, if you're going to call up Auris here in the USA, do you just call that Chicago # on the website, or is there some other more local outfit one should call, like maybe the guys overseeing the actual trials?

I guess what I'm saying is, who do you call? Thanks!

 

[JohnG]

We also have to keep in mind this: as much of a cinderella story as we'd like it to be, Auris is in this for the money at the end of the day. They will not hurry along their process for regulatory approvals in the various agencies to benefit those of us suffering. They're going to make sure every t is crossed, every i is dotted. The paperwork for a regulatory approval is mind boggling.

Which is also why they, and most drug companies, cherry pick the participants very carefully. To some extent, this is a form of fudging data. Because, we know, they will market said drug to a wider audience than said drug was tested on. Ergo...not quite genuine test data (except if you apply it to 7' tall, one-legged, green person with a mole on their ear) that they selected for the trials. Gotta love drug companies. I bet after all is said and done, AM-101 will be marketed for any T sufferer from A to Z. You wait. ..But of course, I hope it does work for every T sufferer from A to Z.

 

[JohnG]

Even if the AM-101 Phase III trials were successful, they would not meet that standard (i.e., the results would not have been independently reproduced), but I would accept them anyway. I would not accept Phase II results as proof of efficacy under any circumstances.
Stephen Nagler

So you just stated you would except possible bad data anyway! From your own article:

"Some major reasons for the high failure rate include misleading or inaccurate information recorded in Phase II trials and ineffective programs that do not provide enough information for moving on to Phase III trials or designing an adequate subsequent experiment. Sometimes Phase II trials suffer because of shortened timelines before approval. Drug development regularly centers on Phase II programs for cutting down the timeline. Due to this, Phase II trials, at times, provide incomplete data or are improperly executed. "

So if phase III have high failures due to phase II inaccurate design and are not independently reproduced by another lab...and may not prove efficacy anyway but still pass, as does happen, you would except it? That is very much why I got ototoxicity, because you guys get most of your info from pharmaceutical companies that give you biased information. That is why it will *never* be a decision between me and my "doctor". I need to see the data and FDA register of complaints against the drug before I accept any "doctor's" opinion. In fact, I'm in the process of filing a complaint for the drug I took. Few doctors follow up on patient complaints to the FDA....very few...so the drug looks squeaky clean.

Though you sound like pulling the company line, you do, indeed, act on bad data. So I ask you this: what defines "proven" From what you described, you have not given anything but a moving, nebulous, target of "proven". So you too should redact what you call "proven".

Quid pro quo

 

[Dr. Nagler]

Though you sound like pulling the company line, you do, indeed, act on bad data. So I ask you this: what defines "proven" From what you described, you have not given anything but a moving, nebulous, target of "proven". So you too should redact what you call "proven".

Quid pro quo

John, you are acting like this is some sort of a contest.

The world - at least the world I live in - is not black and white. It is full of grays. I am simply telling you what I would accept as evidence. You do not have to agree with me, but please do not try to rub my face in it. It makes you look bad.

Stephen Nagler

 

[JohnG]

You do not have to agree with me, but please do not try to rub my face in it. It makes you look bad.
Stephen Nagler

And you look better??? I think the word is....hmmm arrogance comes to mind. But you are right...truce

Indutia!

 

[Dr. Nagler]

And you look better???

I'm not trying to look better. This is not a contest. I have no dog in this hunt. And I really don't care who agrees with me and who doesn't.

I am merely trying to inject a little objectivity into the AM-101 feeding frenzy on this board - because like it or not there are actually two sides to this discussion. And I think folks deserve to see both sides.

Stephen Nagler