AM-101 TACTT1 Results Released

#781
Dr. Nagler said:
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
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Phase III clinical trials are built to statistically prove efficacy. That's the point of them. I was not attempting to suggest that Auris is "cherry picking" patients (they are not). You simply have to meet the criteria defined by their study. Every scientific study has to have a reproducible method to it (meaning a well defined patient population) or else it is meaningless. This does not mean they are trying to falsify data; in fact, they're making it stronger.

I agree. The world is full of grey area. AM-101 most likely will not cure tinnitus for the majority of people. It will lessen it to a degree if it ends up being proven to work.

In my earlier post I just wanted to remind everyone that this will take time to be approved, even if the trials go well as we all hope. Regulatory submissions processes (both in the EU and US) are not quick deals, and no biotech company would risk their ability to make money on getting the treatment out there a little sooner. I'm just pointing out what the reality of the situation is. I stand by my speculation that mid 2016 is the earliest that we can hope for Auris to have this approved, assuming their trials meet their end points.
 
#782
Dr. Nagler said:
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
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On a nice note. I think that folks on this board get it. Auris is a profit centred company with shares of stocks on the exchange. They have been picking patients quite nicely (even in phase III) which is suppose to be more inclusive to represent a more realistic patient group. The data looks good so far, but data can be pruned to look nice. I think folks here get that too. Perhaps we are just optimistic and hope for the best.

And as you know, medicine is not so much a science as an art. Sometimes you get it right...some times you get it completely wrong. We hope phase II,III will catch most errors...and 50% is a good catch...but more slip through the cracks. We hope this system prevents thalidomide of the 1950s...remember that disaster...and that was one of the first big catches of the FDA in that day. So we do catch many with trials...hopefully most dangerous drugs....but not all.

But I guess the question here is, let's suppose this drug doesn't do squat...nada....niche. What will go wrong? Well we can rule out T killing us. If the drug doesn't work, well, we just have T. So then it comes down to the contraindication of the active compound. I think we do have data on that. Then there are the risks to any surgical procedure (intra-tympanic injections in general). So I think folks are discussing the up side and down side here. Perhaps we are getting a little euphoric at times but I think we do know the risks.
 
#783
Hudson said:
Phase III clinical trials are built to statistically prove efficacy. That's the point of them. I was not attempting to suggest that Auris is "cherry picking" patients (they are not). You simply have to meet the criteria defined by their study. Every scientific study has to have a reproducible method to it (meaning a well defined patient population) or else it is meaningless. This does not mean they are trying to falsify data; in fact, they're making it stronger.
.
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I agree with that to a point, but phase III trials have a high failure rate due to poor design and patient selection and end points as pointed out above. The term cherry picking is where the patient selection may not represent the patient the drug will be marketed to. Phase III is designed for efficacy but companies do fail a lot due to poor design. So Auris still has to meet that. And we do see drugs where patient selection was not designed well and did not represent the intended patient population.
 
#784
Sometimes Phase III trials fail because of poor design. Sometimes Phase III trials fail because of problems with patient selection. Sometimes Phase III trials fail because of issues with end points. All that is true.

Phase III trials also fail because no matter how much you might want a drug to be efficacious, it isn't! Or better put, sometimes Phase III trials succeed, but the results of those successful trials are not what one would have hoped for.

Stephen Nagler
 
#785
This is definitely far from a cure. It's a company releasing the drug, and not a University. It's clear that these guys are in it for the money, but that's not to say it won't work. It just means that it won't be the treatment everyone's hoping for. If you think about it, Ketamine is already on the market as a drug for other medical use, and the guy who was going to make the pill form of this drug, disappeared or something. I'm betting that had something to do with Auris losing the "originality" of their "drug," and probably decided they had to inject it into the ear to be able to market the drug as their own. Just a guess.
 
#786
Its nice to have high hopes for this drug since theres none to date that help with T... But after reading through this forum im kinda thinking that unless
This drug comes out on the market im not gonna get my hopes up... Have higher hopes for the vagues nerve stimulation trials..
 
#787
Kimbo Slice said:
This is definitely far from a cure. It's a company releasing the drug, and not a University. It's clear that these guys are in it for the money, but that's not to say it won't work. It just means that it won't be the treatment everyone's hoping for. If you think about it, Ketamine is already on the market as a drug for other medical use, and the guy who was going to make the pill form of this drug, disappeared or something. I'm betting that had something to do with Auris losing the "originality" of their "drug," and probably decided they had to inject it into the ear to be able to market the drug as their own. Just a guess.
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I think the reason they inject is because in this way it is more local, otherwise it wont work. Its the same with eyes - they give you drops that contain the same antibiotics that can be taken orally as well, but are more effective when applied right in the eye. Also, the fact that a certain drug is already on the market doesn't mean that all of its uses have already been discovered.
That being said, no scientist ever said that AM101 is gonna be a "cure" - it was clear all along,, as it only reduces the noise which means it is just a treatment. Also of course everybody hopes, because its the drug coming out the soonest. However I have to say though that considering the speed of science I would consider myself lucky if there would be a treatment for chronic tinnitus in 10 years. Considering that for the past 30 years people have been ssaying that there will be a treatment in 5-10 years I dont know how accurate that is.
 
#791
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:
 
#792
Danil said:
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:
Click to expand...
did your messsage stop by accident? you finished with a :
 
#793
Id put my money into vague nerve stimulation or the autofony. The time this comes out there could even be another drug or other treatment in a phase 1 that could actually be more focused on chronic t
 
#794
Stina said:
did your messsage stop by accident? you finished with a :
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You have right Stina,

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:

"An even more significant predictor of failure was novel mechanism.Even after the patient evaluation process in Phase 2, drugs that used novel mechanisms of action failure more than twice as often in Phase 3 as those that used known mechanisms.And if drugs had both novel mechanisms and less objective endpoints, they failed 70% of the time."

According to another recent article, oncology candidates are particularly risky, with only 8% of candidates achieving approval that completed phase 1.Along the same lines as the McKinsey study, the author cites the Investigational Drug Steering Committee (IDSC).In general, the IDSC:

"encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs," while acknowledging that "objective response as an endpoint and single-arm designs remain relevant in certain situations." "There is a lack of predictability in the way Phase II trials are conducted in cancer because few are done in a comparative fashion."

Similarly, the experts interviewed for the article point out that the key rests in powerful, well-designed phase 2 studies.A great piece (from the author's Alma Mater) addresses the lack of efficacy in Phase 2, and suggests a remedy.

While companies will never be able to eliminate all of the risk in large-scale clinical trials (e.g. some long-term side effects are not foreseeable), hopefully the field as a whole can become more efficient, helping patients and investors alike.While the above data is not perfect or exhaustive and definitely not indicative of future success / failure, it is a good place to begin for any investor interested in development stage firms.In particular, all sources consulted agreed on one thing: phase 2 results are paramount.The implication appears to be that management cannot always be trusted to make the correct decision (possibly because of loss of objectivity about compounds, pressure to deliver on announcements, pipeline incentives, etc.).
 
#795
An effect that the medical researchers often fail to account for, since it isn't addressable by classical statistics, is the need for greater evidence of efficacy for more novel treatments. Treatments that are new, one-of-a-kind, or based on a new idea have a higher failure rate in Phase III because they were tested to the same degree as better understood treatments in Phase II.

As Carl Sagan said, "Extraordinary claims require extraordinary evidence."

Jim
 
#796
Quick question for this board.

AM 101 does not want anyone taking any medication.

I take trazodone at night at times. I have discontinued it for a while now, however there is some nights I could use the help (which I think people with tinnitus understand).

Is it that AM 101 really thinks that taking any drug like an advil or a trazodone would cause super adverse consquences?

What I think is that they do not want anyone taking any drug because it could waterdown the study. They only would want AM 101 in someones system because they would know for sure if it was AM 101 that helped.
 
#798
As I mentioned on another thread, I have an appointment to be evaluated on the 28th of this month for participation in TACTT3. My goal is to be as aware as I possibly can be of any risks of this study before going for an evaluation. My two primary concerns are:

1) risk of permanent hearing loss due to the injection itself, or the drug
2) risk of ear infection due to the injection
​
From what I have read here, it seems like 1 is not very likely at all (around 0% chance), and 2 is a low possibility. Would anyone with more knowledge than I be able to comment on the probability and/or severity of these risks?
​
 
#799
StayPositive said:
As I mentioned on another thread, I have an appointment to be evaluated on the 28th of this month for participation in TACTT3. My goal is to be as aware as I possibly can be of any risks of this study before going for an evaluation. My two primary concerns are:

1) risk of permanent hearing loss due to the injection itself, or the drug
2) risk of ear infection due to the injection
​
From what I have read here, it seems like 1 is not very likely at all (around 0% chance), and 2 is a low possibility. Would anyone with more knowledge than I be able to comment on the probability and/or severity of these risks?
​
Click to expand...

1. The risk of permanent hearing loss is negligible to near impossible. They are perforating your ear drum, and technically hearing issues are always possible with this type of a procedure. However, it is done many thousands of times a year already around the world and has been for years. The hole they will make in your ear drum for the injection will be many times smaller than the hole that is made for putting "tubes" into someone's ears for chronic ear infections.
2. The risk of ear infection due to the perforation is very low, and a lot of it is up to you. Once they perforate your ear drum, don't stick any q-tips in there. Make sure you wear the ear plugs they provide to you when you shower and to avoid getting water in your ears until the hole is closed. If you do that, the chances of you getting an ear infection from this are negligible as well.
 
#804
Willie said:
Would anyone be able to email them for me, please? My laptop is currently getting repaired and sending emails through my phone is a hassle.
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They won't answer patient inquiries on behalf of a complete stranger, I'm assuming. Send the email through your phone. The hassle is worth it, unless you like tinnitus.
 
#807
Willie said:
Would anyone be able to email them for me, please? My laptop is currently getting repaired and sending emails through my phone is a hassle.
Click to expand...

Btw you have had tinnitus since 2010 sso why are you calling anyway? They only accept patients who have had it from 3-12 months. The fact that you had it go louder recently doesn't matter to them, youve still had it for 4 years.
 
#808
To reply. IF someones T became worse through a new event and it was not a "flare up", then the cochelea must be newly reacting to that event. If someones T was 10 db for 12 years and then someone had another event that brought the T up from 10 to 20db in right ear, perhaps the cochelea has execissive activity in it where AM 101 might work for this type of person. the extra 10 db has to come from somewhere right? and perhaps it is coming from the cochlea that has been revived to be much louder. Perhaps Am 101 could put the new fire out.



Nobody knows a thing about tinnitus (neither do I, and that is for sure) but the languange of the AM 101 study says after an event the cochelea overreacts. If someone has a new event that creates a newer louder type of tinnitus for the person, well AM might say the cochelea is overexcited due to this new event. And a new event might be able to be treated.

an opinon- nothing more nothing less.
 
#809
MarkW123 said:
To reply. IF someones T became worse through a new event and it was not a "flare up", then the cochelea must be newly reacting to that event. If someones T was 10 db for 12 years and then someone had another event that brought the T up from 10 to 20db in right ear, perhaps the cochelea has execissive activity in it where AM 101 might work for this type of person. the extra 10 db has to come from somewhere right? and perhaps it is coming from the cochlea that has been revived to be much louder. Perhaps Am 101 could put the new fire out.



Nobody knows a thing about tinnitus (neither do I, and that is for sure) but the languange of the AM 101 study says after an event the cochelea overreacts. If someone has a new event that creates a newer louder type of tinnitus for the person, well AM might say the cochelea is overexcited due to this new event. And a new event might be able to be treated.

an opinon- nothing more nothing less.
Click to expand...
I thought of that too it makes perfect sense, to me anyways.
 

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