Otonomy OTO-413 — Treatment of Hidden Hearing Loss

The fact that the company was started because the Chairman himself is a sufferer is the sort of thing that always gives me hope. For people like that it's not just about a buck, it's really about help suffering people. One more possible aid/cure coming down the pipe. Daddy like.

 

I should have asked this earlier, but what's OTO-413's first goal? Hearing loss or tinnitus? If it's for tinnitus, is it for acute or chronic one tinnitus?

 

OTO-313: tinnitus, definitely acute. May help some people more chronically.

OTO-413: treats cochlear synaptopathy a.k.a. "hidden hearing loss" caused by synapse death (common especially in noise induced cochlear damage). The hope is treating the underlying cause will treat the tinnitus but if you have a different cause (e.g., Middle Ear Damage, TMJ, Meniere's, etc. It's not likely to help). This is for acute or chronic synaptopathy (and for related tinnitus, presumably).

 

It's for hidden hearing loss aka cochlear synaptopathy. But many researchers think that hidden hearing loss could be the cause of tinnitus (although it could be both hair-cell or synapse loss, anywhere where there is reduced auditory input). So it's reasonable to assume that it will benefit those of us with noise-induced tinnitus.

 

Sorry to just throw a link at you, but I found this one helpful.

https://www.otonomy.com/pipeline/

 

OTO-413 is for synapses - AKA speech-in-noise function. There could be benefit with tinnitus too although this has not yet been examined and neither was it something being measured in the primary trial.

OTO-313 is for tinnitus and it is initially being tested on acute tinnitus although it appears it will be tested on chronic tinnitus too.

 

It’s aimed at hearing in noise specifically, and indirectly at hearing loss. The hopes are it will help with other hearing-related ailments as well.

 

Hearing loss called synaptopathy. Hearing-in-noise, specifically.

However, many posting here have provided evidence that point to restoring this type of loss may also treat tinnitus. The tinnitus would likely have to be a symptom of noise induced hearing loss.

 

Has anyone talked about these potential treatments with their specialist?

If there is more than one treatment, we may need further guidance in which potential treatment would best apply to our specific situation. I can see how I would possibly fit into more than one category.

My doctors had differing opinions on what had occurred with my hearing.

 

Many believe that those with tinnitus as a symptom of noise-induced hearing loss or acquired sensorineural hearing loss will likely need both OTO-413 and FX-322 since the damage is likely mixed between synaptopathy and hair cell damage/loss.

It’s likely that even getting one of these treatments will provide some level of relief as hearing is restored. There are anecdotes of FX-322 trial participants noting improved tinnitus. No such anecdotes for OTO-413, yet.

The knowledge of these drugs by ENTs and other hearing specialists vary widely. Some are aware and enthusiastic, others clueless. Likewise the available diagnostics vary widely if at all right now, so most of us will just have to trial treat and see what works.

 

You'd probably be very disappointed to find out just how little clinicians usually follow research (there are exceptions). Instead, they often wait for the new treatment or drug to come out and the pharmaceutical reps come by and train the doctors on the new drug (this is a big part of the marketing budget for new drugs).

They will be trained when and why to use these drugs at that time (and at continuing education conferences which is one reason they are required to keep licenses, but this is still only after the drug is launched).

 

I have noticed I study current research more than most of my doctors. My PCP and specialist both use a program to input symptoms and it gives them a list of potential causes.

 

Same - this condition is debilitating. Lighten or remove it and I'll let the doctor spit in my ear if necessary. Just give me some relief

I wish there was a sad react emoji.

 

I cannot wait to feel the cold steel hit my cochlea! Hurry the F up and approve FX-322 and OTO-413!

 

Right now I'd like them to hurry the F up and confirm that tinnitus is impacted by these drugs.

I know there was some anecdotal evidence on the FX-322, but right now I think we are all assuming, not without reason, that restoring lost hearing will make the tinnitus decrease or go away. A not insignificant part of me is afraid that while these drugs may restore hearing they may not be particularly effective in making my brain stop screeching.

 

We already know about the FX-322 anecdotes but they are measuring tinnitus results with their current trial.

Asking Otonomy about tinnitus anecdotes would be a great Tinnitus Talk Podcast question, though.

 

You are so right, we need a bit more anecdotes about tinnitus improvement and not just hearing improvement before I dare to believe it for real...

 

Just a few more weeks to wait. I can see the headlines now for FX-322: ”20-30 dB restored across frequencies above 1 kHz, tinnitus greatly reduced or eliminated in 87% of patients”.

I’m an F’ing dreamer, man.

 

I also have my doubts.

If effective for tinnitus, all the people who had benefits from FX-322 or OTO-413 should have clearly shown the reduction or elimination of their tinnitus, but it didn't occur (only in some cases it seems that the tinnitus has decreased, but not all or the majority).

 

We don’t know if it was the majority or if it wasn’t though. All we know is some participants reported tinnitus improvement. Some could have had improvement and not mentioned it. Some could have mentioned it but the ENTs didn’t pass on the information because it’s anecdotal and not the main point of the research. We also don’t know how many people actually had tinnitus in the first place.

 

This is true but you could require both drugs in both ears in order to eliminate tinnitus or reduce it. Which we won't know until both of these drugs are out.

 

Where are you getting this information?

 

I don't think Frequency Therapeutics gave any number regarding the percentage of tinnitus patients that experienced improvement. Their focus was on hearing restoration for those with mild to moderate hearing loss. I believe that the majority of people with mild to moderate hearing loss either don't have tinnitus or it is so light it isn't even thought about, so who knows how many of the study cohort have the buzz.

That there was some anecdotal evidence indicating that some of the subgroup with tinnitus reported improved doesn't really tell us if it is as @Philip83 hopes that almost all experienced real improvement or if it is that more disappointing 40ish% with statistically significant improvement (weak tea) that every tinnitus device/treatment seems to have.

 

It has been mentioned in this forum several times that some people showed improvement of their tinnitus (people who were in the hearing loss trial, but also had tinnitus, the fact that some of them improved is what has made Frequency Therapeutics - if I recall correctly - take tinnitus into account for Phase 2 or 3).

In fact why are people here talking about a treatment for hearing loss if this is a tinnitus forum? Because it is believed that this treatment will improve or eliminate tinnitus, right?

 

Patients with “bothersome” tinnitus was an exclusion factor for OTO-413 Phase 1/2. So if they did have it, it would be so mild they may not show significant improvement anyway. Also, no tinnitus measurement (TFI) was used in this trial.

No tinnitus improvement anecdotes have been released/leaked for OTO-413 either.

So we know nothing about how OTO-413 / repairing synaptopathy affects tinnitus.

We do know that participants that received OTO-413 saw an improvement in their hearing on at least 1 measure of hearing.

Many on this forum have speculated that simply improving hearing signal to the brain may reduce the “phantom” sound.

Source:
https://clinicaltrials.gov/ct2/show/NCT04129775

 

They weren't measuring for tinnitus improvement in Phase 1/2 though.

 

The only thing that Frequency Therapeutics said is that they had anecdotal evidence that it helps tinnitus, enough to add it to their exploratory measures.

They gave zero stats (so far they will at the conclusion of the current trial).

This is probably the wrong thread to talk about Frequency Therapeutics in though.

 

Yes, this is true. What I was questioning was that your statement about that ”it didn’t occur” is only a guess at this point, since neither Frequency Therapeutics nor Otonomy has collected any data on tinnitus so far.

@FGG and @Diesel summarized it pretty well above.

 

Otonomy may have put themselves in a cannibalization scenario with OTO-313 for tinnitus. If it turns out OTO-413 treats tinnitus as a symptom of synaptopathy; it reduces the need for a OTO-313 which might be a problem.

One might hypothesize that if FX-322 does indeed produce a significant reduction in TFI by creating new hair cells and thereby improving hearing; it's pretty likely that reconnecting synapses and improving hearing may also have a noticeable affect in tinnitus.

Just one theory.

 

Nice problem to have.