Otonomy OTO-313 — Treatment of Tinnitus

By vehicle, do you mean the placebo contains similar compounds as OTO-313 but no drug? If that's the case, it seems kind of dangerous to have sustained release placebo... I don't know.

 

By vehicle I mean their slow release gel, since it's proprietary. I think they are injecting that + some unknown substance that may look similar to the actual drug.

I agree, having a sustained release placebo is kind of dangerous but it's the only way to do it. I don't know if they can even change their placebo.

 

The problem is there could be an ingredient in the placebo giving an improvement effect temporarily... Thereby making significant results difficult to distinguish. At least that's the case with saline in hydrops in mice.

 

Exactly, OTO-313 is useless for tinnitus because it is not a regenerative drug. Otonomy's only promising drug is OTO-413 because that actually was made for the purpose of restoring synapses, which would in turn improve tinnitus. Otonomy's got it wrong in how they are separating tinnitus and "hidden hearing loss" because they are integrally related, hidden hearing loss directly causes tinnitus. Well I guess we just need to wait a year to see the results of OTO-413 and Pipeline Therapeutics' treatment.

Also, Frequency Therapeutics are convinced that their one dose regiment of FX-322 will work even though the multi-shot didn't. If I recall correctly, FX-322 was shown to regenerate hair cells as well as their neural connections in mice, which is of course a good sign.

 

@Hazel successfully interviewed Otonomy the other week for Tinnitus Talk Podcast. Kindly, @FGG gave her time to prep Hazel. @Markku is now editing the interview, making it ready for publication. Our trusted volunteers are working on the transcription.

It's going to be our longest episode to date, about 90 minutes.

The video version of the interview, sneak peek below, will be exclusively available for our Patrons (those on Patreon.com + recurring supporters here), and will be out about a week before the general public's audio version. Both versions should be out before the end of this month.



Come support our work for as little as $2/month! After Otonomy, we will publishing an interview with Prof. Dirk De Ridder, which has already been recorded earlier this month. Great start to summer!

 

According to Otonomy, OTO-313 is not useless for tinnitus. FX-322 hasn’t shown anything for tinnitus.

 

While I agree that synaptogenesis and hair cell regeneration will be the "cures" for a lot of tinnitus sufferers (most likely NIHL and SNHL), OTO-313 is a powerful NMDA receptor antagonist that actually binds, so there is a pretty good chance it could help a lot of people.

 

Staff edit in red:
@AfroSnowman's post below pertains to us having released the Otonomy interview in video format just moments ago for our Patreons (the email announcement goes out tomorrow). The audio only version will be released over the next week for everyone. In the meantime, if you want to support our work and get the video version, you can ➡️ join our Patreon program here.

Sorry I don't have the biologic vocabulary for this...

So I'm listening to Tinnitus Talk Podcast interviewing Otonomy. It sounds like they assume that early on (< 1 year of onset) whatever chemical is being released can be reduced or stopped from binding - if it's not, this process causes damage to synapses.

If this process is stopped, both the tinnitus and synapse damage stop. Hopefully all is good thereafter.

But personally as a long hauler of having tinnitus for >2 years, and it'll certainly be at least 5 more years before this would have any chance of becoming available, is there any reason that I should care about OTO-313? Is there fundamentally not going to be a drug for me?

 

Could help reduce spikes or additional damage from new acoustic traumas.

 

Awesome.

 

Blah, pretty useless for me then.

 

Would OTO-413 help you then?

 

That's great to hear. Just hope I'm lucky enough to get the real deal and not placebo.

 

Maybe, but who knows. I am one of those people you might have read about that are suspected of having been shot by a microwave weapon, likely Russian. I’ve been extensively studied, scanned, and tested and they can’t determine if it is IHC or OHC damage. I suspect a bit of both but as I regained significant portions of my hearing about 5 months after the attack. Maybe it is mostly synaptic as, from what I understand, OHC shouldn’t come back that long after an incident.

In short, I don’t know what kind of damage is expected from that kind of incident, so even if OTO-413 worked in general, I haven’t got the faintest idea if it would help me.

 

I found it interesting that in the Tinnitus Talk Podcast they pointed to synapses being lost due to "overexcitement" that OTO-313 was trying to reduce. If OTO-313 does indeed show consistent improvement in Phase 2, it may validate that the overexcitement reduced synapse loss leading to less permanent tinnitus or no tinnitus. This outcome may show that for tinnitus where noise was a factor OTO-413 / PIPE-505 restoring synapses may actually provide a meaningful benefit.

Speaking anecdotally, I did notice many years before my tinnitus that I was having trouble hearing in noisy environments. So, for those of us exposed to noise, perhaps hearing-in-noise deficits/synaptopathy is an early indicator for risk of "NIHL tinnitus."

 

I don't know about all of the benefits from OTO-313, but can it work for tinnitus caused by visual snow syndrome?

What do you guys think? I guess it's most likely synapse related hyperactivity in the (AC) auditory cortex & thalamus if you are dealing with tinnitus & visual snow syndrome. And what I heard so far it's a powerful (NMDA) receptor antagonist that can calm down these synapses and related symptoms.

Regards,
Tasty

 

Anyone hazard a guess if OTO-313 might provide some benefit beyond the acute phase?

 

The doctor at the clinic for the OTO-313 trial told me that in the first trial they didn't have enough people to be statistically significant so the one they are doing now with 140 participants is to demonstrate that it not only works but also does/can work on a large scale. Also props to that guy for breaking the ENT doctor mold, super accommodating and nice, and wasn't resolved to rest on his laurels when it came to tinnitus.

He struck me as the type of guy who probably saw patients were suffering and wanted to do his part to help run the trial at his location. He gave OTO-313 a two-year timeframe to get approved or to advance to a meaningful point for approval IIRC, which struck me as a bit optimistic but I think that's what he said. He did seem keen on there being no treatment for cochlear-related tinnitus from noise and seemed to think that that fact would help speed it along if results continued to be good.

They think I'm a good candidate for the trial and I'll probably end up getting my first administration in July, so I'll post my feedback then.

 

This gets touched on in the Tinnitus Talk Podcast. From my recollection they don’t know and their model for how tinnitus works in the brain/auditory system doesn’t particularly suggest that this would be an effective treatment. On the other hand, they don’t entirely discount it, but right now they want to focus on what their theory holds is the most likely responder group.

 

That was a fantastic interview!

Thanks so much @Hazel et al for the effort involved to do these.

 

Thank you Hazel, this is awesome!

 

In the Tinnitus Talk Podcast it was confirmed that the placebo formulation is the exact same as OTO-313 minus the drug, as said in this quote at around 41:42:

"To put this into context, the placebo is the same formulation as OTO-313, just minus the drug, so it's not a difference in if a true placebo and then it's exactly the same material, it just doesn't have the drug in it."​

If this is the case, am I the only one concerned that they are placing extended release placebo in the ear? I do not think it is a good idea to have something that won't do anything to stay in the ear that long. They stated that OTO-313 can last around a month in the ear, so it seems kind of dangerous to have placebo in the ear for that long. This is probably why the placebo had more adverse effects than OTO-313.

I get that they want to make it look the same to the patient, but realistically how will the trial patients know the difference between OTO-313 and some non-extended release injection? Surely there is another way to go about doing the placebo.

 

No concern here. If there were some severe adverse reactions with the extended release gel, it would affect both placebo and drug participants. So, the gel itself would be of safety concern, but it isn't.

As far as worsening of tinnitus being seen by the placebo group, it helps prove that the application of the drug was the differentiator. It shows that where both groups went on living their lives after receiving the drug, OTO-313 continues to reduce the onset of tinnitus, while placebo didn't do anything. If they used too different of a gel as placebo, the integrity of the study would be called into question.

 

I got noise-induced tinnitus in March of this year from my headphones being on blast for half a second. I emailed one of the locations regarding OTO-313 and they mentioned I would be a good candidate, but am a little concerned.

Does anyone know if this gel makes your ear feel like there's liquid inside your ear? I would hate to have that feeling in my ear for the rest of my life.

 

It does, but it’s temporary.

 

I have an opportunity to participate in the trial. Should I do it or is the risk too great?

 

Everybody with tinnitus should be in this trial. That’s my opinion.

 

It does help progress the science. As long as I pass the screening visitation, I should be getting the injection on 7/21/2021.

 

I’ve been following this drug more than the others; please keep me updated, good luck.