Otonomy OTO-313 — Treatment of Tinnitus

[EkkoMusic]

@Sentinel, thoughts? Would love your take on this now that the cat's out of the bag.

 

[dd314]

Hence the nerve damage. OTO-413 is intended to heal the synapses related to hearing instead of the hair cells.

I put zero stock in OTO-413 for healing tinnitus. They don't know what really causes this monster. There's also different levels of abstraction at the mechanistic level of what causes it. Whether you got slapped in the ear, or fired a shotgun, or took too much aspirin, those are all different "causes" at one level off abstraction, but at the olfactory perception level, it's the same mechanistic "cause". We don't know much beyond that, and neither do researchers apparently.

Hopefully Kv7 openers can come to the rescue.

 

[LAnative]

I put most of my stock in OTO-413.

I look at it very simply: Shotgun bang, nerves fried, tinnitus starts. Heal nerves, tinnitus ends.

Looking forward to Q4 results. I am positive.

 

[Sentinel]

@Sentinel, thoughts? Would love your take on this now that the cat's out of the bag.

Yeah sure.

It felt a bit like a kick in the stomach when I got the news yesterday morning. I sympathize with all of you as someone who took part in this trial and completed it. There's a lot of talk about the placebo effect going on and it makes me wonder if I didn't receive some sort of truly miraculous placebo effect that's lasted a long time.

I'm going to leave an audio file below that you can listen to since I don't much feel like typing and feel more conversational at the moment.

 

[KoolKat]

Somebody put a positive spin on this ASAP please. Otonomy can recover, right? This won't slow down the OTO-413 trial, right? Somebody will partner up with them, right? Is there any way they can modify OTO-313 and continue or is it a complete failure like AM-101?

OTO-313 wasn't intended to directly deal with the cause, which even we all kinda knew that it's in the brain, not the ear , and OTO-413 deals more with the brain, right? And there's other things trying to treat tinnitus as well, correct?

I think once we get something where we can visually see tinnitus, I think trials for curing tinnitus will be more easier, right?

But again somebody put a positive spin on this, please.

 

[AnthonyMcDonald]

And there's other things trying to treat tinnitus as well, correct?

The only thing I actually have my eyes on that might help a lot is XEN1101 as it addresses the root cause of most types of tinnitus (noise induced, DCN hyperactivity).

I never really had much hope for OTO-313 as it doesn't address this issue at all. Maybe only some people have NMDA receptor hyperactivity but it definitely IMO isn't the root cause. OTO-413 might do something with restoring synapses but again, I don't think hearing restoration will help much (this is only my opinion, we really don't know if it will or not).

All in all I think that the OTO-313 trial failed due to its horrible design. They dug their own grave. It might work as a drug, and I don't doubt it does a bit for some, but the structure and exclusion criteria was awful and they doomed their own trial.

 

[Brian Newman]

Somebody put a positive spin on this ASAP please. Otonomy can recover, right? This won't slow down the OTO-413 trial, right? Somebody will partner up with them, right? Is there any way they can modify OTO-313 and continue or is it a complete failure like AM-101?

OTO-313 wasn't intended to directly deal with the cause, which even we all kinda knew that it's in the brain, not the ear , and OTO-413 deals more with the brain, right? And there's other things trying to treat tinnitus as well, correct?

I think once we get something where we can visually see tinnitus, I think trials for curing tinnitus will be more easier, right?

But again somebody put a positive spin on this, please.

I was one of the most optimistic people here, but now I don't really know. I was extremely positive about OTO-313. OTO-413 seems like it works but I'm not going to bank all my hope on any of this stuff anymore. I know there will be something eventually but this ear stuff is incredibly complex. There's still hope but I can't put all my hopes in the medical field anymore. I'm going to be homebound for a very long time. I'm going to have to find ways to live with this. We're all going to have to find ways to deal with what we're experiencing. OTO-313 is a lost cause unfortunately.

 

[Toby1972]

I thought I was so close to relief from my behemoth. I could probably have participated in a Phase 3. Now it's becoming increasingly clear to me that nothing will help us ever, the interaction of hearing / nerves / brain is probably just too complex to be able to be helped by any remedies.

I've managed to manage my life somehow with psychological help, but not with the fact that my noise is getting worse every quarter. Only prospect of a life with very limited quality. Holy shit.

 

[Gb3]

Now it's becoming increasingly clear to me that nothing will help us ever, the interaction of hearing / nerves / brain is probably just too complex to be able to be helped by any remedies.

Why do people say this? We know they have stopped tinnitus with deep brain stimulation. We know some people who get cochlear implants have their tinnitus resolved.

 

[attheedgeofscience]

Pretty incredible that a full decade of clinical trials still hasn't yielded any tangible progress. That's pretty much all I have to say. Best wishes to everyone.

 

[Diesel]

Yeah sure.

It felt a bit like a kick in the stomach when I got the news yesterday morning. I sympathize with all of you as someone who took part in this trial and completed it. There's a lot of talk about the placebo effect going on and it makes me wonder if I didn't receive some sort of truly miraculous placebo effect that's lasted a long time.

I'm going to leave an audio file below that you can listen to since I don't much feel like typing and feel more conversational at the moment.

Now that the trial is over and dead, and although I was one of the members here protesting you talking about your experience during trial, it would be nice to know if you got the drug or not.

 

[Ava Lugo]

Lol - ok bye. It seems this issue that we suffer from is too hard to solve.

This really sucks

 

[Sam Marksmen]

No one should underestimate the power of greed. Imagine big pharma looking at Otonomy and its crashing stock.

Then think how much the big pharma made on the COVID-19 vaccine and the advancement in medicine it brought them. There's an average of 20 percent of just America, not to mention the world that's an untapped tinnitus market.

I've read posts here from 2015 about people hopeful in OTO-313. Otonomy has made such a huge investment and advancement. Isn't the failure of OTO-313 just evolution to a path for a cure?

Listening to the Tinnitus Talk Podcast and hear Otonomy talk about OTO-313, they seemed very optimistic. Now I have doubts about OTO-413 however.

Treatment for stuff like Parkinson's seems to be the best bet as it's in the brain. Elon Musk, save us with Neurolink! You need a lot a lot of money to fix this, big pharma or Musk look hopeful.

 

[lusiol]

This hit hard. Maybe not as much as FX-322 but not that far.

Even if I have always been agnostic and sometimes anti-religious, I will start to believe in god and pray at this point.

 

[dd314]

OTO-313 DOES do something.

The probability that Phase 1 was a false positive is incalculably small. Something weird happened.

https://pubmed.ncbi.nlm.nih.gov/34629442/#&gid=article-figures&pid=fig-2-uid-1

 

[Sentinel]

it would be nice to know if you got the drug or not.

I've contacted the clinic and requested the information. They are reaching out to Otonomy and will call and email with a response.

I inquired about their OTO-413 trial they were running when I was there and they told me it has been completed and that only a few other locations are still running trials.

 

[NYCGuy]

The worst thing about this is I lost all hope. I also lost a lot of money investing in Otonomy's stock. I saw a few people getting this treatment and doing better, but it seems it was time healing their ears.

 

[ColinUK]

OTO-313 DOES do something.

The probability that Phase 1 was a false positive is incalculably small. Something weird happened.

https://pubmed.ncbi.nlm.nih.gov/34629442/#&gid=article-figures&pid=fig-2-uid-1

If it did something, it would have made it to Phase 3. No way Otonomy would abandon it and basically sink their company if it did something.

Also the trouble with these readouts is they are from short term tinnitus sufferers who can have natural massive improvement from initial onset... Pair that with you thinking you're getting a wonder drug and boom, improved mental attitude improvement in TFI.

Why all these things go from super promising to nothing, it's just such a difficult rollercoaster to keep riding. Science, please just give us something.

 

[Diesel]

If it did something, it would have made it to Phase 3. No way Otonomy would abandon it and basically sink their company if it did something.

Also the trouble with these readouts is they are from short term tinnitus sufferers who can have natural massive improvement from initial onset... Pair that with you thinking you're getting a wonder drug and boom, improved mental attitude improvement in TFI.

Why all these things go from super promising to nothing, it's just such a difficult rollercoaster to keep riding. Science, please just give us something.

I'm going to quote one passage from the recent press release:

"These results were unexpected with a much higher placebo response than observed in the prior Phase 1/2 study," said David A. Weber, Ph.D.​

Frequency Therapeutics said the exact same thing with their Phase 2A failure with regards to primary outcomes. Now, they dug into it and released that it was clear that patients had likely suppressed word scores to get into the trial. Which, in turn, caused the placebo group to perform better than expected.

In my opinion, if patients with measurable hearing loss are willing to do something unethical to get an experimental drug, people who are brand new to tinnitus CERTAINLY will do the same.

Therefore, either their trial design wasn't robust enough to filter out patients that could create a good placebo control, the onboarding testing (TFI) isn't good enough, or there truly was a placebo effect at play once the population scaled.

No matter what, Otonomy is running out of money, and can't spend it on a do-over Phase 2 for OTO-313 like Frequency Therapeutics has been fortunate enough to do with FX-322. They had to make a tough (but correct call) to move forward with OTO-413, which still has a clear path to Phase 3. Who knows, maybe they'll learn from whatever happened with OTO-313 and pick it back up later when funds are available.

 

[ThomasF]

No matter what, Otonomy is running out of money, and can't spend it on a do-over Phase 2 for OTO-313 like Frequency Therapeutics has been fortunate enough to do with FX-322. They had to make a tough (but correct call) to move forward with OTO-413, which still has a clear path to Phase 3. Who knows, maybe they'll learn from whatever happened with OTO-313 and pick it back up later when funds are available.

This is why pushing for funding from ideally any source, but particularly governments, is important. These companies getting to take second shots at these meds as well as new meds will lead to progress if not a cure. Perhaps a reformulated OTO-313 or a second run in testing.

People being desperate for treatment to the point of fudging tests means this is extremely important. There's so much potential in Otonomy for it to go to waste.

 

[Nick47]

I'm going to quote one passage from the recent press release:

"These results were unexpected with a much higher placebo response than observed in the prior Phase 1/2 study," said David A. Weber, Ph.D.​

Frequency Therapeutics said the exact same thing with their Phase 2A failure with regards to primary outcomes. Now, they dug into it and released that it was clear that patients had likely suppressed word scores to get into the trial. Which, in turn, caused the placebo group to perform better than expected.

In my opinion, if patients with measurable hearing loss are willing to do something unethical to get an experimental drug, people who are brand new to tinnitus CERTAINLY will do the same.

Therefore, either their trial design wasn't robust enough to filter out patients that could create a good placebo control, the onboarding testing (TFI) isn't good enough, or there truly was a placebo effect at play once the population scaled.

No matter what, Otonomy is running out of money, and can't spend it on a do-over Phase 2 for OTO-313 like Frequency Therapeutics has been fortunate enough to do with FX-322. They had to make a tough (but correct call) to move forward with OTO-413, which still has a clear path to Phase 3. Who knows, maybe they'll learn from whatever happened with OTO-313 and pick it back up later when funds are available.

I think it's likely some patients lied to get accepted to the trial, over egging their TFI just to meet the severe category and, once in, they gave real scores.

 

[Sam Marksmen]

I just feel so bad as some people were saying they were going to kill themselves, but that OTO-313 gave them hope. I have no idea what will happen now when they read about it failing.

I just can't believe the Tinnitus Talk Podcast here, where the founders were saying they had a 40 percent or so success rate. If it did, it would have gone to Phase 3. Should we trust Otonomy at all anymore? Have they hit a wall altogether? And if tinnitus is a brain thing, would OTO-413 be a better avenue ultimately anyway?

 

[Diesel]

I just feel so bad as some people were saying they were going to kill themselves, but that OTO-313 gave them hope. I have no idea what will happen now when they read about it failing.

Not to be an ahole about it... but OTO-313 was never for the chronic cases that most of us have been living with for years and years. It was a treatment to mitigate the damage occurring in brand new cases that becomes permanent. Anyone on here with tinnitus for over a year is already basically in the permanent state.

The only positive that this could have had for the chronic sufferer is to validate specific parts of the biology that are getting "overexcited." So, it may have helped to mitigate the occurrence/severity of spikes.

 

[attheedgeofscience]

Listening to the Tinnitus Talk Podcast and hear Otonomy talk about OTO-313, they seemed very optimistic. Now I have doubts about OTO-413 however.

Well, the efficacy of OTO-313 was evaluated using the TFI score (which is fully subjective). OTO-413 is evaluated using speech-in-noise testing (which is objective). But the result can of course be influenced in one direction (but not the other ) i.e. pretending not to hear something which actually was audible. But this would require ill-will. So the OTO-413 trial should be less susceptible to bias.

There is also the question of how to select clinical trial participants. Here the best approach would be to offer participation to those whose etiology is already known rather than to sign-up those who have heard about a given clinical trial, and who wish to enroll in it, but have not yet disclosed their patient details. In-a-nutshell: if you advertise rather than hand-pick your candidates, then you may end up with a messy patient population.

Before Auris Medical decided to move into another pharma-space, they were actually working on a way to objectify tinnitus assessment (as far as I know). The reason for this is (now) ever more clear: in order to conduct a placebo-based clinical trial you need to stop relying on self-assessment.

My best guess is that OTO-313 probably works, but they are unable to prove that it works. Which is a tragedy...

 

[Toby1972]

Inject me with the OTO-313 stuff. It doesn't need 158 participants who are undecided, it only needs me. I am a classic tinnitus sufferer (noise trauma).

I have massive, constant tinnitus 24/7, it shivers left, right, 3D everywhere. Any minimal improvement I would attribute to OTO-313.

Cost of the study: Nearly zero. Knowledge: 100%.

 

[Brian Newman]

Well, the efficacy of OTO-313 was evaluated using the TFI score (which is fully subjective). OTO-413 is evaluated using speech-in-noise testing (which is objective). But the result can of course be influenced in one direction (but not the other ) i.e. pretending not to hear something which actually was audible. But this would require ill-will. So the OTO-413 trial should be less susceptible to bias.

There is also the question of how to select clinical trial participants. Here the best approach would be to offer participation to those whose etiology is already known rather than to sign-up those who have heard about a given clinical trial, and who wish to enroll in it, but have not yet disclosed their patient details. In-a-nutshell: if you advertise rather than hand-pick your candidates, then you may end up with a messy patient population.

Before Auris Medical decided to move into another pharma-space, they were actually working on a way to objectify tinnitus assessment (as far as I know). The reason for this is (now) ever more clear: in order to conduct a placebo-based clinical trial you need to stop relying on self-assessment.

My best guess is that OTO-313 probably works, but they are unable to prove that it works. Which is a tragedy...

You're right. What a tragedy. OTO-313 probably does help a little. Yet they can't prove it. Many things probably work but can't be proven. Most severe tinnitus sufferers would try it even if it had a 5% chance of helping. Especially it not being as expensive as stem cells, most people would definitely try it. My noxacusis is way more of an issue but I was definitely looking forward to getting my tinnitus down. Looks like we will be waiting a while longer.

 

[DimLeb]

It's funny how we were saying that 2022 was going to be a big year for treatments, but as it now seems, all has been pushed to 2023 or indefinitely further. I wonder if the same story will happen every year, just like the past decade or so it has happened.

 

[SmallRonnie]

It's funny how we were saying that 2022 was going to be a big year for treatments, but as it now seems, all has been pushed to 2023 or indefinitely further. I wonder if the same story will happen every year, just like the past decade or so it has happened.

If you go back and look at comments about the same topic from years ago, you will see people are always hopeful of a treatment soon.

It's obviously a tough task but at least there is hope for a potential treatment.

 

[Wrfortiscue]

It's funny how we were saying that 2022 was going to be a big year for treatments, but as it now seems, all has been pushed to 2023 or indefinitely further. I wonder if the same story will happen every year, just like the past decade or so it has happened.

Yep. Seems we all have to just find ways to deal with it vs. hoping a cure is coming. I mean hope is a powerful thing, but I think many would just benefit to accept it and try to move on. I believe all of us right now will set the right path for others in the future. They thank us for our sacrifice

Man I sound grim lol.

 

[DimLeb]

They thank us for our sacrifice

This became real dark real fast lol.