Otonomy OTO-313 — Treatment of Tinnitus

I think they need funding first. If they meet their target of around $60k however and do not progress then, it will be an issue.

 

Is there a copy of the transcript of the discussion regarding the phase 2 results? It appears to be encouraging but not too exciting... I'm always cautious to the responders being, what, 40-50%...

 

40-50%... was this not also the responder rate that Lenire has? But here they just used a single injection and in the next trial they want to increase the dosage.

What strikes me a bit is that 7/18 from the placebo group got mild to severe tinnitus and hearing loss worsening. What kind of placebo did they use? Was it ototoxic?

 

That's a good question. Although, all the participants were still acute and those things can worsen in the acute stage. Would love to know what they used though.

 

Is OTO-313 for people who've had tinnitus for less than 6 months?

 

It is implied that OTO-313 is for people with fresh tinnitus <6 months. But they are going to do a 2nd trial for people with tinnitus older than 6 months, just to be sure if it works for chronic tinnitus as well.

 

Where does it say that??? How strange, a placebo causing worse tinnitus and hearing loss from a placebo?? How devastating for the volunteers to help out in a trial that could help millions to get a placebo that worsens it... absolutely wrong, I could understand worsening with an experimental drug because that's the risk, but placebo?!?!?

 

I wonder weather the injection itself caused a worsening.

 

I’m quite shocked that there was an improvement in tinnitus for this trial whereas @ChrisBoyMonkey got a worsening. I would not expect a placebo to cause a worsening in tinnitus. Either ChrisBoyMonkey got a placebo or he got the real drug but experienced an adverse reaction to it.

 

This is mentioned here on page 12:

I am wondering this, too. This injection through the eardrum seems to be standard ENT practice, but we know some standard ENT tests make some worse.

 

I was wondering weather the injection did some harm mechanically. I don't know what they inject in placebo, water or a saline solution maybe, but the mechanical act of the injection might trigger a worsening in a sensitive ear perhaps.

 

Chinmoku,

That's what I think. Add stress, fear, and anxiety after seeing the first effects. I had an experience a few months ago because of something on the eardrum without importance but I noticed that the tinnitus was rising and I was losing my hearing. In the end it was silly but the fear made me believe something else.

 

Yea could be. I was expecting this trial to fail after we found out ChrisBoyMonkey had a worsening but then to hear that 40-50% had improvements in their tinnitus was shocking but to still hear that they got improvements on both Day 29 and Day 57 is awesome news.

I still believe to treat tinnitus you need to restore the hair cells and synapses. This drug seems to reduce tinnitus but not fix the underlying hair cells and synapses.

 

Has it been proven that there is no underlying structural improvement with this treatment, even very slight minor repair.

 

Its mechanism of action is on the NMDA receptor. This shouldn't have a regenerative effect.

 

I think that you are actually right. While it is evident that hearing loss treatments terrifically aid the tinnitus symptoms (eg: cochlear implants) it is also well proven that there are some people with no hearing loss on the chart who will also experience trouble from tinnitus. Hence with studies strongly identifying that you can have issues with both hair cells and synapses in relation to tinnitus this then needs to be dealt with to totally resolve the issue with tinnitus troubles.

The trial evidence only demonstrates the tinnitus improvement and doesn't provide data on whether it also assisted with the other parts such as hair cells and synapses. It would be very interesting to see whether it assisted either of these or whether it delivered some other treatment/repair which was what helped it to improve individuals' tinnitus.

This treatment therefore seems pretty promising for now, however I am still of the opinion that this will probably not be the total treatment needed to resolve tinnitus as compared to the other two medications which seem majorly more promising to resolve not just tinnitus but the wider issues stemming from tinnitus in Hough/OTO-413 and OTO-322.

 

Trust me, if OTO-313 regenerated hair cells or synapses, OTO-313 would publish/advertise that fact. It would have shown up in pre clinical and they would be testing for auditory changes.

The NMDA receptor is not on a regenerative pathway. If the drug works, (and I suspect it would be more valuable acutely), it's due to blocking the NMDA receptor which is involved in the neuroinflammation at onset.

 

I get this impression too & that's why I think it won't work for chronic, established tinnitus. While it's good news it may be helpful for new tinnitus, in a way it's not because the market for tinnitus may become less smaller for chronic tinnitus and reduce the incentive for biotechnology companies to find a cure for chronic and as you know tinnitus is a high risk field in the business world.

What baffles me though is that in their investor report they talked about the size of the tinnitus market that included chronic cases and that may mislead investors if it's only thought to target acute tinnitus. The market gap between them is significant. It would interesting if Tinnitus Talk could get a Q&A with them.

 

Quite a good insight, thanks. I was not sure whether they were allowed to disclose details about stuff not 'focused' or 'expressed' as being tested during the trial. You learn something new everyday.

 

I could be going down the wrong path possibly, however I have a feeling that a large percentage of individuals who will experience chronic tinnitus also have hearing issues. I therefore tend to wonder whether this treatment subsequently may get run out by other options to do with synapse and cell repair. Thus OTO-413 might actually also eliminate this as it will help with 2 in 1 and therefore it is pointless to just take another medicine which provides no assistance.

 

As with my theory stated before that I believe to get rid of tinnitus you need to restore the underlying issue in the ear such as hair cells and synapses.

 

It would really surprise me if this had much of an effect chronically but it would be nice to be wrong in that case.

 

It's worth noticing that Auris Medical's AM-101 had the same mechanism of action, that failed to meet its endpoints in phase 3. It's a bit of a weird one, Auris Medical seem determined to get AM-101 to the market and I think I recall they are changing the endpoints to get it approved. Still, 2 biotechs, Auris and Otonomy, believe this can work... at least for acute tinnitus.

 

It is way too coincidental that tinnitus issues seem to get more pronounced with reduced hearing. Helping these with auditory stimulation has demonstrated to significantly improve tinnitus.

Thus I feel that these treatments are a dead end as they simply seek to not actually resolve the underlying problem. Pretty sure the treatment research really supports this too so far.

 

Where do we people who have had tinnitus for years have to look for some hope? FX-322? Hough Ear Institute? When is it realistic to expect them to be available?

Yes, these questions are boosted by a monster spike.

 

Well the question remains to be if even synapse regeneration and hair cell regeneration will completely resolve tinnitus. So far it seems the best bet, followed by Prof. Thanos Tzounopoulos, followed by Neuromodulation, and then this.

 

I think FX-322 is our best chance at getting rid of our tinnitus. Since tinnitus is measured in Phase 2a clinical trials we should know more about it whether it helps with tinnitus or not when they are done with this phase.

 

Absolutely, drugs that treat the underlying cause are what will treat chronic tinnitus.

As far as when it depends on if your cochlear problem is hair cell (FX-322) or synapse (OTO-413, Hough, PIPE-505). Also depends on the FDA. The time line should be a lot more known early next year.

 

I certainly think that for the majority of people, restoring hearing will hopefully cure or at least greatly reduce their tinnitus issues/suffering. However, I think it is a bit short sighted to think of these other avenues of treatment as a "dead end", there are a large number of people whose tinnitus is caused or exacerbated by other conditions (not just hearing loss), and though I have high hopes for things like FX-322, it isn't going to be the golden ticket for all of us here.

I say this as someone who suffers from hearing loss that fluctuates somewhat dramatically, and with tinnitus that does the same. In my personal case there is often little correlation between the amount of auditory stimulation and the amount of tinnitus. I'm likely an edge case, but point being - I think that it's worth the time and effort to look at treatments such as these.

 

Thanks. Yea I get that NDMA isn't regenerating anything but I'm curious if someone could have some connected synapses that have no/reduced functionality but with say with this drug and its reduction in environmental inflammation mean a handful of said synapses become or improve in signal conductivity.

Not sure how you could test this... Maybe create artificial synapses and test under these conditions with measurements on a synapse by synapse basis? Has that already been done?