Otonomy Otividex Fails in Phase 3 Ménière's Trial

[grate_biff]

That's a bit like asking why do some people experience temporary tinnitus and permanent tinnitus. Excellent question. I wish I knew the answer.

No. It was not a good question!
I was trying to act naively to make a point!(thanks though)

Listen, like you, I don´t know anything really. But I have done my research like most here.
I´m sure you have too, but you really kind of take to the negative and hide behind being a realist, like I´ve said before. And you seem to have no problems making bold statements about your views either.

You admit doing this because you hope someone will tell you different, and I can understand that.

There are many theories regarding acute vs. chronic tinnitus and if the brain are able to unlearn it, should the inner ear pathology be restored.

Acute vs. chronic: I think it comes down to the scope of the damage. I´ve experienced three really bad acoustic traumas in my life. The first two lingered for some month, then vanished. The third time it stayed and it is also much more severe/piercing, than the first two I experienced. I think the brain has the capacity to adapt and maybe also learn to use other resources from the cochlea(recruit adjacent healthy HC) to find some sort of balance. It could also be the brains natural filter-mechanisms (GABA) that can only stagger a certain degree of neuronal excitement over time. Maybe there is a significant difference between the two and that one will only respond to a drug within a certain timeframe. I read that a lot, so there is probably something to it. But when it comes to the synapses f.i. it's said they can be medically recovered for decades. Of course this would not help either if T is for life no matter what we will be able to repair.

When the damage is to severe for the brain to overlook and out of options, T will sustain, and ironically this is also a result of the brain seeking balance.


Can it be unlearned: T is a complex brain phenomenon, yes, but so is any kind of experiencing pain. When the issue responsible for the pain is fixed/healed, it goes away. Why would this not apply when repairing the inner ear?
Plasticity is not a one way street either. Its a term for the brains ability to change and adapt to its surrounding environment. Environment being our body. And memory? Surly it will remember how it was previous to damage then? And if not to say, the state of the brain with out damaged ears is probably its "preferred" state as well. Not having to compensate for anything. I choose to believe that, anyway.

I am a realist as well, as -well- informed- as- I -can-realist. Maybe with a little sugar on top.

The vexing thing for me is the time-consuming ordeal for science to play around with a compound before recognizing any benefits. Especially for drugs that is not even supposed to go in your bloodstream, but rather your cochlea fluids (talking about Frequency Therapeutics here). That is the killer for me!

 

[VRZ78]

Everytime there is a new thread this debate brain vs ears comes up it's really annoying. If you could stick to the topic that would be nice. No one knows anyway.

 

[jer]

As I have stated this again and again, once they stop testing this on mice and instead test it on any animal that more closely resembles a human. Only at that point will we see some good progress in drug testing.

 

[grate_biff]

Everytime there is a new thread this debate brain vs ears comes up it's really annoying. If you could stick to the topic that would be nice. No one knows anyway.

I don´t think it´s that irrelevant to discuss this seeing a drug fail.
Either way, if my post did anything(not getting my hopes up) with the receivers constant negative posting, I did us all a favor.

 

[Markku]

As I have stated this again and again, once they stop testing this on mice and instead test it on any animal that more closely resembles a human. Only at that point will we see some good progress in drug testing.

Phase 3 trials (including this one) are done with human subjects, and actually previous phases were too as is normal (after the pre-clinical trials).

More on how it works here:
http://www.centerwatch.com/clinical-trials/overview.aspx

 

[Aaron123]

It's been remarkable how quickly this thread went off topic.

Some more information: http://www.nasdaq.com/article/otono...ails-key-trial-shares-nosedive-20170830-00346

Interesting quote (with bold added):

"At this point, we have no explanation for the unequivocal negative result," the company said on a call with analysts, adding it planned to further analyze the data to investigate what went wrong.

Otonomy said it would also suspend its ongoing European trial in Meniere's disease patients.

Before Wednesday's trial results, analysts had largely believed both trials would succeed.

Cowen & Co analyst Ken Cacciatore said on Tuesday that if approved, Otividex could account for a $500 million market opportunity in the United States alone.

The delivery technology used by Otividex is already used by Otonomy'sFDA-approved antibiotic for an ear infection that generated about $300,000 in second-quarter sales.

Otonomy also withdrew its annual operating costs forecast, pending an internal review of its product pipeline.

And here: http://www.xconomy.com/san-diego/20...-loss-drug-after-phase-3-flop-shares-routed/#

And a pretty grim sounding title here: https://www.fool.com/investing/2017/08/30/heres-why-the-market-is-eviscerating-otonomy-inc-s.aspx

The most concerning thing about this outcome is the utter and complete failure. This wasn't even close. It raises questions about the design of either the Phase 2 or the Phase 3 trials.

 

[Greg Sacramento]

The company has little insider ownership on forms 3 & 4. Institutional holdings is also weak, but if management truly believed and not make believe, they would had owned more shares outright. Bio techs like this one, always reinvent and stay in business as management always cashes a paycheck.

 

[Jim51042]

Is this going to threaten Otonomy's corporate survival? Are there alot of similarities in this failed compound to OTO-311 and OTO-411?

 

[3ri0w]

Patience! When it's closer to the beginning of the phase II trial. You won't miss it!

However, as was announced, they're also undertaking a general review of their product pipeline so the direction of the Q&A may or may not change a bit depending on the outcome of the review.

Will it be in Finland ^__^

 

[Aaron123]

Now we are getting somewhere: https://endpts.com/otonomy-staggered-by-an-ugly-phiii-failure-for-lead-pipeline-drug/

I didn't realize that the Phase IIb trial had basically failed and that Otonomy had changed the endpoints for the Phase III trial.

If this approach to changing the end points of a trial sounds familiar, it might be because Auris did the same thing following disappointing AM-101 trial results. Among other things, they elevated the TFI from a secondary endpoint to a primary endpoint. We will have to wait and see how that works out...

 

[Casper]

Is this going to threaten Otonomy's corporate survival? Are there alot of similarities in this failed compound to OTO-311 and OTO-411?

Unfortunately, I'm not sure that they'll survive this. From the article linked above (emphasis mine):

"Based on these results, we are immediately suspending all development activities for OTIVIDEX including the ongoing AVERTS-2 trial. In addition, the company is undertaking a review of its product pipeline and commercial efforts to identify opportunities to extend its cash runway and build shareholder value."

I interpret the above as that they'll have to be more conservative going forward, perhaps trying to generate revenue from their existing drugs rather than investing in new ones. Taken from here:

An application that could expand Otipro's addressable patient population to include those with swimmer's ear, which is currently under FDA review, could boost Otonomy's top line a bit next year.

And finally, from the same article:

Even if it succeeds, though, it's hard to see the company climbing out of the crater Otividex's trial failure just made.

So yes, I wouldn't hold my breath waiting for Otonomy to be the company that comes through with the cure for Meniere's.

 

[jeff W]

Ha ha ha ha ha!

 

[jer]

@Markku yes I know that phase 3 trials are done on human subjects. The initial research for drugs is always done on lab rats or mice. This is to test if the drug would have even a chance of having a positive reaction at all.

What I was saying, was that they should not do the initial testing of the efficiency of medicine on lab rats before it goes into any phase trial, but on something that resembles the human physiology closer. This is so we wont have these...." It worked great in the lab rats/mice, I don't know what went wrong in human testing issues anymore. As mice/rats and us differ is so ways, it just seems insane to keep testing medicines intended for us on them.

 

[Rubenslash]

@Markku yes I know that phase 3 trials are done on human subjects. The initial research for drugs is always done on lab rats or mice. This is to test if the drug would have even a chance of having a positive reaction at all.

What I was saying, was that they should not do the initial testing of the efficiency of medicine on lab rats before it goes into any phase trial, but on something that resembles the human physiology closer. This is so we wont have these...." It worked great in the lab rats/mice, I don't know what went wrong in human testing issues anymore. As mice/rats and us differ is so ways, it just seems insane to keep testing medicines intended for us on them.

Frequency Therapeutics tested their product on primates.

 

[acufenero]

Frequency Therapeutics tested their product on primates.

Actually, on tissues from mice, non-human primates and a human donor.

 

[DebInAustralia]

If your tinnitus is caused by damaged nerves or ihc/ohc, and these would be restored, and the brain would be picking up signals again, why wouldn't it disappear.

Like with alcohol, if you're addicted, and you get none, you quiver. Over time, this effect will decrease and you'll stop quivering. I believe, similair will happen after hearing restauration. The old normal will be picked up and tinnitus will fade.

Because there's an argument that even after damaged auditory pathways have been restored, maladaptive plasticity has occurred; maintaining tinnitus.

 

[Paulmanlike]

I was reading an article from rTMS before (going off subject but related to above comments) that it was more likely successful in people with recent onset tinnitus rather than long term. A possible explanation of this being that maladaptive plasticity has long set in.

 

[jer]

Well, that is very good news then. Finally one company who has their head screwed on straight.

 

[wizman]

Another trial failing!
It seems easier to research to invent the time machine than to solve the problem of T.
With this I would get back before noise exposure time

 

[Fabrikat]

I'm starting to suspect that these trials are just job creation schemes for private labs. Sigh!

 

[jer]

Again, this was not for tinnitus but for Meniere's. This had to do with reducing vertigo attacks, that's it folks! Nothing to do with us.

 

[jeff W]

I'm starting to suspect that these trials are just job creation schemes for private labs. Sigh!

They are not looking for a treatment for Meniere's, they are looking for something that can be "passed off" as being efficacious and be resold over and over again for a large profit. Steroids, not a clue as to how they work and they want to stick them in diseased ears, no thanks. I hope this company sinks hard, it can be like the Lehman Brothers collapse and serve as a warning to other biotech corps who want to peddle us mickey mouse treatments. I nearly vomitted with laughter when this came up on my feed! lol

 

[jeff W]

Fuckin cowards blocked their twitter and shut their facebook,

 

[Randall Smith]

Fuckin cowards blocked their twitter and shut their facebook, View attachment 13559

What that means? Why did they shut down their facebook and twitter?

 

[Paulmanlike]

What that means? Why did they shut down their facebook and twitter?

Because they're a laughing stock and have many angry investors.

 

[VRZ78]

They are not looking for a treatment for Meniere's, they are looking for something that can be "passed off" as being efficacious and be resold over and over again for a large profit. Steroids, not a clue as to how they work and they want to stick them in diseased ears, no thanks. I hope this company sinks hard, it can be like the Lehman Brothers collapse and serve as a warning to other biotech corps who want to peddle us mickey mouse treatments. I nearly vomitted with laughter when this came up on my feed! lol
View attachment 13558

Wow man I think you need to educate a bit more on the subject.
Excuse me but what you wrote is the stupidest thing I've read here...
And what is the fuss with the steroids? This is the only treatment that seems to actually do anything for now, if taken within 24 h after onset of course.

Otonomy is one of the companies that has the highest chance of curing or reducing tinnitus with their OT-4XX program. Hopefully with this failed trial and the disappointing results of the AM trials they'll focus more on their OT-4XX program.

 

[jeff W]

Wow man I think you need to educate a bit more on the subject.
Excuse me but what you wrote is the stupidest thing I've read here...
And what is the fuss with the steroids? This is the only treatment that seems to actually do anything for now, if taken within 24 h after onset of course.

Otonomy is one of the companies that has the highest chance of curing or reducing tinnitus with their OT-4XX program. Hopefully with this failed trial and the disappointing results of the AM trials they'll focus more on their OT-4XX program.

Ha ha ha ha ha ha ha ha. Go buy some shares so! Quick before the bell closes.

Could you please educate me on the proposed mechanism of action in the use of steroids on sudden hearing loss btw this was for Ménière's Disease not shl.

 

[Paulmanlike]

I think the main concern here is investor confidence. It's been virtually destroyed overnight.

 

[VRZ78]

Ha ha ha ha ha ha ha ha. Go buy some shares so! Quick before the bell closes.

Could you please educate me on the proposed mechanism of action in the use of steroids on sudden hearing loss btw this was for Ménière's Disease not shl.

They are anti inflammatory. They keep the inflammation down.

Anyway. Everyone has his own opinion...

 

[Berik]

Because there's an argument that even after damaged auditory pathways have been restored, maladaptive plasticity has occurred; maintaining tinnitus.

Based on eg below quote I believe restoration of hearing damage solves the problem.

In fact, I've personally witnessed an in-law relative who has had Tinnitus since he fought in Vietnam discovering that by wearing advanced hearing aides that restore high frequency perception, the Tinnitus faded away to the point that he was disturbed by the silence for the first time in 40 years.

https://www.tinnitustalk.com/threads/popping-in-ears-improved-hearing.9148/