Otonomy OTO-413 — Treatment of Hidden Hearing Loss

[OptimusPrimed]

This is what's so maddening to me, given we just saw this happen with FX-322. I guess it was maybe too late as Otonomy had already begun their trial design but I can't help but feel like they shot themselves in the foot if the placebo group is actually what brought them down. (Perhaps it wasn't - someone please correct me).

What evidence do we have that the same trial issues from FX-322 and OTO-313 will not occur with OTO-413?

OTO-413 has had better results than OTO-313 so far. The synapses readily respond to the medication and reconnect to the hair cell terminals. Easier to measure success too.

 

[SmallRonnie]

This is what's so maddening to me, given we just saw this happen with FX-322. I guess it was maybe too late as Otonomy had already begun their trial design but I can't help but feel like they shot themselves in the foot if the placebo group is actually what brought them down. (Perhaps it wasn't - someone please correct me).

What evidence do we have that the same trial issues from FX-322 and OTO-313 will not occur with OTO-413?

Someone else, @attheedgeofscience I think, already said something about the OTO-413 trail being designed better. I don't know what it is but the info is in this forum if you care to search.

 

[in_LA]

OTO-413 has had better results than OTO-313 so far. The synapses readily respond to the medication and reconnect to the hair cell terminals. Easier to measure success too.

These should reconnect to the brain once grown, right? Sorry, I'm not good with science stuff. I fear that they'll grow but not connect.

 

[kingsfan]

OTO-413 has had better results than OTO-313 so far. The synapses readily respond to the medication and reconnect to the hair cell terminals. Easier to measure success too.

Once the neurons die from excitotoxicity, I don't think there would be much that OTO-313 could help with. Therefore, OTO-413 is definitely the drug to have fingers crossed for.

 

[Damocles]

FX-322 v10.8.0.4

View attachment 51386

 

[CRGC]

From ClinicalTrials.gov page:

Exclusion Criteria:

[...]

• Subject self-reports bothersome, subjective tinnitus and is consistently aware of their tinnitus throughout much of the waking day.

So much for our chances to be part of the trial.

 

[Brian Newman]

From ClinicalTrials.gov page:

Exclusion Criteria:

[...]

• Subject self-reports bothersome, subjective tinnitus and is consistently aware of their tinnitus throughout much of the waking day.

So much for our chances to be part of the trial.

True but this is good. There will be no desperate people to affect the trial, trying to get in for tinnitus, causing a flop like FX-322. People with hidden hearing loss are not suffering like the people here. I wish we could all get this drug right now, but this is a good thing for Otonomy.

 

[ThomasF]

True but this is good. There will be no desperate people to affect the trial, trying to get in for tinnitus, causing a flop like FX-322. People with hidden hearing loss are not suffering like the people here. I wish we could all get this drug right now, but this is a good thing for Otonomy.

The desperate have ruined things in the past.

 

[Brian Newman]

The desperate have ruined things in the past.

Yup, even though I have catastrophic noxacusis, I'm not going to try and lie to get into FX-322 or OTO-413 trials. I need those drugs badly but I'm not going to risk the entire trial and the future of a drug I may or may not get (I could get placebo). If I had the exact criteria they were asking for, couldn't hurt, but again, there's a chance you'll get placebo.

 

[IndyMLVC]

Yup, even though I have catastrophic noxacusis, I'm not going to try and lie to get into FX-322 or OTO-413 trials. I need those drugs badly but I'm not going to risk the entire trial and the future of a drug I may or may not get (I could get placebo). If I had the exact criteria they were asking for, couldn't hurt, but again, there's a chance you'll get placebo.

I'm always on the lookout for new trials. I have *several* debilitating ailments (that, unfortunately, work in concert with one another) and I'm always completely honest with the people running the trial. I'm never going to bend the truth or flat out lie to get into something. It's not worth screwing up the entire study over for something that *MIGHT* help me.

 

[SmallRonnie]

All of these hearing regeneration trials are having massive difficulty with trial design as it is. So much of tinnitus/hyperacusis varies naturally that placebo groups are always going to have high positive results.

At least OTO-413 has a better trial design than OTO-313.

I did see some new trial was asking for people who only have stable tinnitus but you really are relying on people just being honest which is less than ideal. I can seriously understand why people will lie to get into these trials.

 

[ThomasF]

All of these hearing regeneration trials are having massive difficulty with trial design as it is. So much of tinnitus/hyperacusis varies naturally that placebo groups are always going to have high positive results.

At least OTO-413 has a better trial design than OTO-313.

I did see some new trial was asking for people who only have stable tinnitus but you really are relying on people just being honest which is less than ideal. I can seriously understand why people will lie to get into these trials.

It is really cruel to lie to get into a trial. The effects are severe after doing so. Not only are your results not reliable but the difficulty in finding appropriate testing subjects is already substantial and adding a monkey wrench like that is not only shooting that person in the foot but as well extending the time of misery we all will experience. I genuinely think they need some type of criminal psychologist to help screen subjects. Tell when they're lying about their tinnitus and boot them from the program. I want us all one day to be cured but that isn't going to happen with people constantly putting their suffering above the well being of everyone else dealing with this inane condition. When the device for objectively measuring tinnitus is available that will hopefully screen out people with tinnitus where they shouldn't be and prove they have it for where they're needed.

I'm not immune to this behavior though, I sometimes believe I have Meniere's despite the ENT I saw last year telling me I do not. I lie to myself hoping that SPI-1005 will help me with that. Perhaps its utility exists elsewhere and can aid my tinnitus differently but I'm not confident in it. One day a true treatment will exist and one day a cure. We won't get there if people like myself will be obstacles to progress instead of pushing it forward. When we choose to put ourselves ahead of progress we hurt so many others it's impossible to comprehend.

 

[antonio77]

I'm always on the lookout for new trials. I have *several* debilitating ailments (that, unfortunately, work in concert with one another) and I'm always completely honest with the people running the trial. I'm never going to bend the truth or flat out lie to get into something. It's not worth screwing up the entire study over for something that *MIGHT* help me.

The problem is that it doesn't matter; many of us can be very honest but it is enough that several are not to completely spoil the study.

You feel very helpless when this happens because you can't do anything.

 

[SmallRonnie]

It all comes down to how they assess the patients. The speech in noise test for OTO-413 does seem like a solid test.

I just noticed tinnitus is an exclusion criteria of this trial. I wonder why that is. It would be unfortunate if this drug healed hearing loss but didn't heal tinnitus. I was kind of assuming any of the regenerative type drugs would be good for anyone who has tinnitus or hyperacusis from loud noise exposure.

 

[Pero1234]

True but this is good. There will be no desperate people to affect the trial, trying to get in for tinnitus, causing a flop like FX-322. People with hidden hearing loss are not suffering like the people here. I wish we could all get this drug right now, but this is a good thing for Otonomy.

They should not have disclosed this but kept this a secret exclusion criterion.

This just results in people with bothersome tinnitus to downplay or right about lie about their condition to get in.

If they didn't write this as exclusion criterion, these people would openly mention it, so they could still be excluded.

 

[Brian Newman]

They should not have disclosed this but kept this a secret exclusion criterion.

This just results in people with bothersome tinnitus to downplay or right about lie about their condition to get in.

If they didn't write this as exclusion criterion, these people would openly mention it, so they could still be excluded.

That's a good point.

 

[ThomasF]

They should not have disclosed this but kept this a secret exclusion criterion.

This just results in people with bothersome tinnitus to downplay or right about lie about their condition to get in.

If they didn't write this as exclusion criterion, these people would openly mention it, so they could still be excluded.

Desperate people will lie under any circumstances. Having experts at spotting liars on a psychological level is a good filter to weed these people out of the testing groups. Until tinnitus itself can be objectively measured via some sort of tool or scan at least.

 

[AxEars]

It all comes down to how they assess the patients. The speech in noise test for OTO-413 does seem like a solid test.

I just noticed tinnitus is an exclusion criteria of this trial. I wonder why that is. It would be unfortunate if this drug healed hearing loss but didn't heal tinnitus. I was kind of assuming any of the regenerative type drugs would be good for anyone who has tinnitus or hyperacusis from loud noise exposure.

I think the goal is to remove those who are attempting to enter the trial for their tinnitus and not hearing loss. If the treatment is successful in treating hearing loss itself but the tinnitus crowd is unaffected, then the tinnitus crowd ruins the trial.

It's clinically correct to try to fix actual hearing loss first, and then tinnitus. Tinnitus patients want to put the cart before the horse here. It's understandable as to why, but it could ruin an actual potential treatment.

 

[SmallRonnie]

I think the goal is to remove those who are attempting to enter the trial for their tinnitus and not hearing loss. If the treatment is successful in treating hearing loss itself but the tinnitus crowd is unaffected, then the tinnitus crowd ruins the trial.

It's clinically correct to try to fix actual hearing loss first, and then tinnitus. Tinnitus patients want to put the cart before the horse here. It's understandable as to why, but it could ruin an actual potential treatment.

That does make sense. There's probably a good chance that a drug that helps hearing loss would also help a large number of tinnitus cases.

Are the results for the latest trial on OTO-413 coming out some time soon?

 

[Diesel]

That does make sense. There's probably a good chance that a drug that helps hearing loss would also help a large number of tinnitus cases.

Are the results for the latest trial on OTO-413 coming out some time soon?

We have to remember that these companies first and foremost live and die by the success of their trials. So designing a good trial is really critical to getting a drug to approval.

A major goal determining a clinical trial's success is the ability to control inputs by reducing variables that create outliers in the final outputs, which can unexpectedly ruin a trial. In the case of hearing loss, there are a ton of variables between each patient that enters the trial, any one of those variables could cause an issue in meeting the primary outcomes of the trial, and either cause it to fail or require a do-over (expensive and high risk.)

Considering these companies live and die by the design of their trials; most likely, a patient with "bothersome tinnitus" presents some type of risk to the trial's success. Therefore, they decided to exclude patients with tinnitus.

While I also agree that there's a good chance OTO-413 can help the population with noise-induced tinnitus (because hearing-in-noise issues share the same underlying classification), it's probably better for the success of the drug reaching the patient; it's better to exclude tinnitus for now. I'd rather find out in the future through people here trial-treating an approved product, as opposed to participants in the trial using unsavory methods to gain entry to trial, making a drug that might actually work unaccessible because they created outlier data and the trial failed.

 

[AxEars]

That does make sense. There's probably a good chance that a drug that helps hearing loss would also help a large number of tinnitus cases.

Are the results for the latest trial on OTO-413 coming out some time soon?

Trial ends at the end of the year. Cleaning up the data could take another few months. We should look towards mid-2023 for results the latest (and not to get our hopes up too quickly for a fast report).

Then Phase 3 would begin, which could be another full year of the trial.

It's why 2025 is such an important year. If any of these trials are successful, they go to market by 2025-27. Once one of them figures it out, the competition will be on to grab a part of a market that is guaranteed to be around forever. Humans will always lose their hearing.

We just need to keep going

 

[SmallRonnie]

Trial ends at the end of the year. Cleaning up the data could take another few months. We should look towards mid-2023 for results the latest (and not to get our hopes up too quickly for a fast report).

Then Phase 3 would begin, which could be another full year of the trial.

It's why 2025 is such an important year. If any of these trials are successful, they go to market by 2025-27. Once one of them figures it out, the competition will be on to grab a part of a market that is guaranteed to be around forever. Humans will always lose their hearing.

We just need to keep going

I'm not going to get my hopes up too much since I don't want to be too disappointed if it fails.

All of these companies talk about how the market will only be growing. The world is much more noisy now with increased use of headphones and AirPods.

This drug does sound like it has better chances of passing than OTO-313 did. Just need to stay distracted until one of these are actually released.

 

[SmallRonnie]

We have to remember that these companies first and foremost live and die by the success of their trials. So designing a good trial is really critical to getting a drug to approval.

A major goal determining a clinical trial's success is the ability to control inputs by reducing variables that create outliers in the final outputs, which can unexpectedly ruin a trial. In the case of hearing loss, there are a ton of variables between each patient that enters the trial, any one of those variables could cause an issue in meeting the primary outcomes of the trial, and either cause it to fail or require a do-over (expensive and high risk.)

Considering these companies live and die by the design of their trials; most likely, a patient with "bothersome tinnitus" presents some type of risk to the trial's success. Therefore, they decided to exclude patients with tinnitus.

While I also agree that there's a good chance OTO-413 can help the population with noise-induced tinnitus (because hearing-in-noise issues share the same underlying classification), it's probably better for the success of the drug reaching the patient; it's better to exclude tinnitus for now. I'd rather find out in the future through people here trial-treating an approved product, as opposed to participants in the trial using unsavory methods to gain entry to trial, making a drug that might actually work unaccessible because they created outlier data and the trial failed.

Thanks for your detailed response. The designs of these trials do seem to be very important indeed.

I would guess it probably wouldn't be hard to get this drug to try and treat tinnitus if it ever does hit the market anyway.

 

[SmallRonnie]

If any of these trials are successful, they go to market by 2025-27.

That's three of them that are that close, is it? Frequency Therapeutics, Otonomy, Sound Pharmaceuticals?

 

[Nick47]

Trial ends at the end of the year. Cleaning up the data could take another few months. We should look towards mid-2023 for results the latest (and not to get our hopes up too quickly for a fast report).

@AxEars, the trial is finished as far as I am aware, with results due in the 4th quarter of this year.

 

[AxEars]

We have to remember that these companies first and foremost live and die by the success of their trials. So designing a good trial is really critical to getting a drug to approval.

A major goal determining a clinical trial's success is the ability to control inputs by reducing variables that create outliers in the final outputs, which can unexpectedly ruin a trial. In the case of hearing loss, there are a ton of variables between each patient that enters the trial, any one of those variables could cause an issue in meeting the primary outcomes of the trial, and either cause it to fail or require a do-over (expensive and high risk.)

Considering these companies live and die by the design of their trials; most likely, a patient with "bothersome tinnitus" presents some type of risk to the trial's success. Therefore, they decided to exclude patients with tinnitus.

While I also agree that there's a good chance OTO-413 can help the population with noise-induced tinnitus (because hearing-in-noise issues share the same underlying classification), it's probably better for the success of the drug reaching the patient; it's better to exclude tinnitus for now. I'd rather find out in the future through people here trial-treating an approved product, as opposed to participants in the trial using unsavory methods to gain entry to trial, making a drug that might actually work unaccessible because they created outlier data and the trial failed.

You nailed it on the head, Diesel. That's what it's all about.

 

[AxEars]

@AxEars, the trial is finished as far as I am aware, with results due in the 4th quarter of this year.

Thanks, Nick. Missed that detail. Even better news!

 

[Nobody19]

Trial ends at the end of the year. Cleaning up the data could take another few months. We should look towards mid-2023 for results the latest (and not to get our hopes up too quickly for a fast report).

Then Phase 3 would begin, which could be another full year of the trial.

It's why 2025 is such an important year. If any of these trials are successful, they go to market by 2025-27. Once one of them figures it out, the competition will be on to grab a part of a market that is guaranteed to be around forever. Humans will always lose their hearing.

We just need to keep going

Please properly inform yourself before saying things like this and giving people hope that this drug has a possibility to release in 2025. There will NOT be a Phase 3 trial yet. Direct quote from their Q2 results:

Otonomy intends to initiate a dose-ranging Phase 2 efficacy trial in hearing loss patients expected to start in the first quarter of 2023.

Source: https://investors.otonomy.com/news-...rts-second-quarter-2022-financial-results-and

 

[AxEars]

Please properly inform yourself before saying things like this and giving people hope that this drug has a possibility to release in 2025. There will NOT be a Phase 3 trial yet. Direct quote from their Q2 results:

Source: https://investors.otonomy.com/news-...rts-second-quarter-2022-financial-results-and

You're right, I wasn't clear. I've said in other threads that 2025-27 is an important timeframe, because if any company's tinnitus clinical trials currently going on prove successful, those years would be the ballpark range for it to be available. I should have said I was speaking in general terms about all trials and not specifically OTO-413

I'm a firm believer that something will be available before 2028, even if it works for 30% of the tinnitus population.

 

[Justin Mills]

So it looks like there are other places working on developing drugs to regenerate synapses, other than Otonomy and Pipeline Therapeutics. I guess it's just a matter of time, although who knows how many years. Well @AxEars thinks it'll be another 6.

But I think it's important to keep in mind it's not just about tinnitus, it's also about restoring hearing fidelity and quality. We should want both, and probably that's the only way to do it, since tinnitus most commonly arises due to hearing damage that results in hearing "loss":

Mass Eye and Ear Researchers Awarded $12.5 Million NIH Grant to Continue Hidden Hearing Loss Research

Drug therapy to repair cochlear synaptopathy - Associate Professor Andrew Wise & Dr. Sherryl Wagstaff