Otonomy OTO-313 — Treatment of Tinnitus

Sound Pharmaceuticals. Here's the thread:

Sound Pharmaceuticals (SPI-5557 & SPI-1005)

 

Sound Pharmaceuticals. There is a thread on here regarding their progress. I updated it today.

Meniere's drug that averaged 30% reduction in TFI for tinnitus is in Phase 2.

It also works for hearing restoration.

Again, it will work better for some, rather than being an all encompassing treatment.

 

This is the big one. In my own personal opinion of course.

 

None of those are targeting tinnitus though, just hearing loss, right? I understand that maybe restoring hearing will help but none are being tested for tinnitus.

@Padraigh Griffin, is XEN1101 being tested for tinnitus?

 

They don’t even know what or if there is a time table for chronic tinnitus. First it was 3 months, then 6 months, now a year. They have no clue.

 

Doesn't seem like it's even getting tested for tinnitus? How are you going to persuade a doctor to give it to you then? I see you posting in the Sound Pharmaceuticals thread too about SPI-1005. SPI-1005 is being tested for Meniere's, so unless you have tinnitus caused by Meniere's, it will probably have little/no effect on most people here.

Am I missing something here, because, to me, it seems like you are grasping at straws for treatments that are not even aiming to treat tinnitus?

 

This is correct.

 

Two words. OFF LABEL. For example Clonazepam is approved as an anticonvulsant and for the treatment of panic disorder but is used primarily for a wide ranger of anxiety conditions. Off label prescriptions are as common as muck and a well known aspect of the medical community. For example Seroquel and Mirtazapine are used off label for insomnia. The list is endless. Trazodone (an older tricyclic antidepressant) for sleep.

BTW, Retigabine is being tested for tinnitus by Professor Thanos Tzounopoulos at Pittsburgh University. Plus I am certain that neurotologists will prescribe Ebselen if it proves efficacious for tinnitus. It has reduced tinnitus by 30% in clinical trials for Meniere's. The likelihood is that it will work for a certain cohort of tinnitus sufferers and certainly those with Meniere's.

Now please point out with facts how this is ‘clutching at straws?’

The world's leading tinnitus researcher prescribes Clonazepam and Deanxit both ‘off label’ for the treatment of tinnitus.

I am sure he and other doctors will be open to prescribing more efficacious and safer drugs to treat tinnitus OFF LABEL.

That is incorrect. See above for more facts. Off label prescribing is well known. Obviously you missed the memo.

https://en.wikipedia.org/wiki/List_of_drugs_known_for_off-label_use

Notice the presence of Retigabine on this list.

Also check out user reviews for Clonazepam on Drugs.com.

A total of 20 off label uses. Take for example 89 reviews for restless legs syndrome.

I thought you were ignoring me. I'm getting bored of ‘schooling you’ on basic facts. We definitely don't get along so let's just ignore each other, thanks. I can't be bothered anymore.

 

My question is simply what does one year mean? I probably have had tinnitus for close to 40 years, but at a very low level. The Moderna COVID-19 booster sent my tinnitus into the stratosphere. That was 4 months ago. So do they consider my having had it for 40 years? 4 months? These are questions that they will need to work out.

 

They mean a one year window when a patient goes from having no tinnitus, to an acute event (noise-induced), to then having a complaint of tinnitus at the doctor. There hasn't been any comment on treating chronic cases beyond a year since initial onset by Otonomy. They have however reiterated that tinnitus transitions from an acute state where there is hyperactivity at the synapses in the cochlea. This is what OTO-313 is intended to treat, by "modulating" the hyperactivity. The tinnitus then moves to a chronic stage where it becomes "in the brain." Which likely means that the synapses and/or hair cells have "died off" and the brain is experiencing a "phantom cochlea" type chronic event i.e.: "missing signal".

Otonomy's position aligns with Dr. T and other chronic tinnitus research as well that has been presented by other firms/institutions. It's also visible in their data from the Phase 1/2 for OTO-313. No data shows a patient go from significantly bad tinnitus to "zero" - indicating a comprehensive treatment. They definitely do better than placebo, supporting their hypothesis, but all the patients still have some form of chronic tinnitus. So, synapses did indeed not return to a normal state and/or hair cells died from the participant's initial incident. This implies that the "phantom cochlea" theory may be slightly more valid.

What I, and others have speculated, is that if you're in a "stable tinnitus" state, then you're most like in the "phantom cochlea" state. A new insult to your cochlea from noise may hyperactivate new cells/synapses that OTO-313 may treat within an acute timeframe. Otonomy isn't going to touch this as it would be incredibly hard to control in a trial setting. So, it will probably be trial and treat for doctors.

In a future state where someone like you might be experiencing a spike in their tinnitus; an ENT may prescribe a dose in an effort to mitigate your tinnitus worsening permanently. Could it have been applied for a COVID-19 vaccine spike? I don't see why an ENT would decline it as an option.

 

Otonomy initially trialed the drug at six months and then a year. They don’t know if it works for chronic cases.

 

I wouldn't be surprised if after years of tinnitus that both sources (cochlea and brain) are involved. Which means you can treat both individually. Just speculating here, but I wonder if a combination of OTO-313 and Dr. Susan Shore's device could bring an 8-9/10 chronic tinnitus down to a 0.5-2/10. Will be exciting to see how it plays out and we'll know soon how well Susan's device works. I'm surely up for trying both if Susan's device also shows effectiveness compared to placebo.

 

A few doctors have been quoted on this forum that they believe a likely cure for tinnitus will involve multiple treatment types. Stem cells, potassium channels and molecular therapies. All attacking the problem from different directions.

 

There is no evidence for 'chronic' sufferers yet, but it might certainly work better for cohorts. A lot of researchers believe there is multiple causes of tinnitus. Susan Shore’s clinical trial with 400 participants will give us great information for causes of tinnitus. If a majority of her trial participants show response, then we certainly know the DCN is involved and Otonomy won't treat that.

 

Thanks, Diesel, very informative. My tinnitus has been at about a 2 for a very long time. If I can just get it back to that level, or even a 3 or 4 I'd be feeling a lot better.

Of course, those of us affected by COVID-19 or a COVID-19 vaccine will be out of luck by the time this med gets authorized by the FDA, assuming it does...

 

Yeah sorry that’s been the outcome for you. I’m not eliminating OTO-413 as a possible treatment for some types of chronic tinnitus. If OTO-313’s success proves that the source of the noise-class tinnitus is indeed synaptic, then OTO-413 at high enough doses could help treat chronic cases.

 

I think it’s reasonable to assume they started with early onset as it’s the hypothetical easiest group to impact. Their goal is to get a drug to market as soon as possible, after all.

 

Fingers crossed, my friend!

They need to do so, and fast. Their cash burn is $43 million per year, which means they will run out of money by Q2 2023, assuming they don't raise another round of funding...

 

Indeed, trial results this year are critical. They’ll raise more with no problem if favorable.

 

Yes that’s true. They have even said that. I don’t know why @Diesel keeps saying that it is only for acute cases. They simply don’t know. The whole phantom cochlear theory is simply just a theory, just like all the other theories they have got wrong about tinnitus.

 

I use acute because that’s the state that the patients are in that they are recruiting. See the ClinicalTrials.gov page. It is written in the inclusion criteria:

“Subject has early-onset subjective unilateral tinnitus that is persistent (consistently aware of their tinnitus throughout much of the waking day)”

Early onset = acute stage.

They also aren’t testing OTO-313 beyond 1 year of onset, which is acute based on established tinnitus standards. I’m def hopeful that it will be effective for longer, but they aren’t interested in extending beyond a year anytime soon.

Who exactly are the “they” that are getting the theories wrong? Shore? Doctor T? The scientists at Otonomy and at hearing research labs in universities? They’ve all postulated that a phantom effect is a possible cause of tinnitus for some cases, particularly SSNHL/NIHL.

 

They're going by the current view of tinnitus, which says it starts in the ear ("peripheral") and then moves to the brain ("central"). Research started to break it down like this after it was found that cutting the auditory nerve didn't always eliminate tinnitus. So researchers believed that it must "move" to the brain after a given period of time. However, they don't know when this happens - and I would say they don't even know if this happens, it could be there are different types of tinnitus.


Slide from Otonomy's R&D Day Slide Deck (see section starting at slide 16)

During their last earnings call Otonomy again stressed they didn't know when tinnitus went from peripheral to central - they even said it could be years, no one knows. My personal belief is that tinnitus doesn't move, there's simply different causes for it - we may know soon enough though if it turns out a drug like this doesn't work for long time suffers.

From what I've found, this paper is the one that defines chronic tinnitus as being more than 3 months, and acute tinnitus as being less than 3 months. That's probably where Otonomy and Auris Medical got their definitions from. Auris Medical's AM-101 was tested on people with tinnitus for less than 3 months (AM-101 worked similarly to OTO-313 but was way weaker) and OTO-313 originally had a similar aim, though Phase 1/2 included 2 groups: less than 3 months, and 3-6 months. They believed it would work best for the "less than 3 months" group, but instead it worked best for the "3-6 month" group.

How they setup Phase 3 will depend on the results for Phase 2. If the drug shows no signs of decreased effect for the 6-12 month group we'll probably see them widen the range for Phase 3.

 

I also subscribe to this theory - on the one hand cutting auditory nerve doesn't resolve, but then we also are told some people that get cochlear implants experience improvement. For others, hearing aids help, but an equal number had no success. End of the day, if any of the potential treatments being discussed on these threads are approved, I'll be trying them all!

 

The study published about Phase 1 did mention that acute patients were higher responders, but they also said that bad severity was also a higher responder. What's the intersection there? Tinnitus is usually loudest right after the insult. For what it's worth, I had a nasty case of COVID-19, unvaccinated, and it only seemed to make mine worse for a week or so. Got super sick, even passed out on my feet from the fever.

 

I'm still fascinated by the study where it worked for 95% of patients. Many other studies come up with a ~50% rate, but one surgeon---JL Pulec, who is now deceased so we can't ask him---reported NINETY FIVE FUCKING PERCENT SUCCESS. Although that on unilateral tinnitus with accompanying deafness, so not quite the common case.

Cochlear nerve section for intractable tinnitus

I went back and read the Retigabine review thread and it wasn't really a slam dunk. There was one guy that said it reliably brought his 7/10 to a 1/10, but that's the only guy I saw that said anything like that. The thread reminds me of Lenire with slightly more success.

 

Pretty sure Phase 1 was all acute cases 6 months and under.

 

I'd never seen that study. Whatever happened to it? Those results are excellent.

I too have read the Trobalt thread and felt that many many more noticed improvements with continued used. It is hard to follow but that was my take from it.

 

Intratympanic Administration of OTO-313 Reduces Tinnitus in Patients With Moderate to Severe, Persistent Tinnitus: A Phase 1/2 Study

"Subgroup analyses were performed and showed differences in favor of OTO-313 for the following subgroups: age less than or equal to median age (57 years) at baseline, tinnitus etiology of sensorineural hearing loss and age-related hearing loss, 3 to 6 months tinnitus duration, 76 to 100 baseline TFI overall score, and 41 to 70 dB hearing loss at baseline (see Table, Supplemental Digital Content 2)."​

As opposed to what? I don't know...

 

They lived happily ever after, appreciating the great privilege of unilateral deafness without tinnitus? I don't know, but I assume that.

Found one of the cases, he got a job and did presumably live happily ever after.

Cochlear Nerve Section for Intractable Tinnitus

 

Isn't that the latest they've tested to date? They've been very clear that this is the group they believe will be most likely to show results and get a drug to market ASAP. And that it doesn't mean they don't think it can work for durations beyond.