Otonomy OTO-413 — Treatment of Hidden Hearing Loss

Discussion in 'Research News' started by Michael Larsen, Jan 9, 2018.

    1. d'Wooluf

      d'Wooluf Member

      Tinnitus Since:
      2010
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      unknown
      Formal musical training is believed by some to improve speech understanding. Google 'auditory training'.
       
    2. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
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      20+ Years of Live Music, Motorcycles, and Power Tools
      When I Googled "auditory training", the entire first page has topics on training hearing when hearing aids are required, or therapies involving hearing loss where hearing aids are not yet required. Nothing relating to music, musicians, singing, musical instruments, or anything of the like.

      There is evidence that formal musician training helps musicians to better pick out and interpret voices in a noisy environment. It turns out it has to do more with their brain’s ability to interpret minimal instrument signal in a noisy environment.

      Personally knowing several musicians and learning of their experience with hearing loss/tinnitus, it seems like @tommyd87 may also have a good explanation for excluding musicians. Perhaps it is both?
       
    3. d'Wooluf

      d'Wooluf Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      unknown
      When the topic of auditory training has come up in other places a common response has been you'd be better off doing formal musical training. A similar goal but musical training works better. That's the tenuous link.

      Musical Training for Auditory Rehabilitation in Hearing Loss

      They would exclude a violinist in a string quartet for noise exposure but take a drummer in a rock band?
       
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    4. Nobody19

      Nobody19 Member Benefactor

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Clubbing
      Apparently you can raise your levels of BDNF (the compound of OTO-413) naturally by working out (Wikipedia has a summary on it).

      Brb going to spend some hours on my treadmill!
       
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    5. star-affinity
      Wishful

      star-affinity Member Podcast Patron Benefactor

      Tinnitus Since:
      1993, increase in 2020, then new in 2021
      Cause of Tinnitus:
      Unsure about the first. Too many beers? Music during sleep.
      Did it help? :)

      If anything I perceive my tinnitus as louder in conjunction with cardio vascular exercise – at least it doesn't do anything to make it quieter. But maybe it takes time for the BDNF to have any effect in the ear. Wonder how much exercise we need for it to be optimal without having to spend too much time? :dunno:
       
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    6. Tau
      Probing

      Tau Member

      Location:
      Europe
      Tinnitus Since:
      2019
      Cause of Tinnitus:
      2019-Concert, 2021-headphones/acoustic trauma at 110dB,16kHz
      Same here, must be the increased bloodflow. I am trying Noopept, a nootropic that supposedly increases BDNF levels in your CNS. 3 weeks in, I am still getting worse. I think we need very high levels of neurotrophins to regenerate the lost synapses.
       
    7. Nobody19

      Nobody19 Member Benefactor

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Clubbing
      The pressure in my ears has improved, but I doubt the little bit of exercise I've had helped :p

      No change in tinnitus, which I don't expect after many years.
       
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    8. Nobody19

      Nobody19 Member Benefactor

      Tinnitus Since:
      2012
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      Clubbing
      Otonomy will give a presentation about OTO-413 next week:

      https://investors.otonomy.com/news-...presentation-oto-413-clinical-results-aao-hns
       
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    9. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

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    10. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
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      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      It's not a do-over, it's an extension. I think it's a smart move on their part tbh. They're able to build on what already looks promising, and use the additional data to construct better parameters for a Phase 2. Which should help reduce the likelihood of failure, and help them to better identify the ideal responder for any future trials.

      Imagine if the guys over at FREQ did this with their Phase 1/2. We probably would have seen the shitshow of a Phase 2A collapse.

      Bottom line, extending it now might save them a boatload of time and resources needed to get the drug through future trials.
       
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    11. patorjk
      No Mood

      patorjk Member Benefactor

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      Several reasons
      In Otonomy's most recent press release they mention that Dr. Volsky (one of their investigators in the trial) was scheduled to give a "presentation of previously disclosed clinical results from the successful OTO-413 Phase 1/2 trial at the upcoming American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS) Annual Meeting to be held in Los Angeles October 3-6, 2021".

      I couldn't find any info about that talk online, so I reached out to Otonomy to see if they could provide me with the slides that were used in the talk. Remarkably they sent them right over. I've attached them to this post.

      I don't believe there's anything we haven't seen before, and most of these seem to be repurposed from their corporate presentation, but it's a good summary of everything we currently know about OTO-413.
       

      Attached Files:

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    12. patorjk
      No Mood

      patorjk Member Benefactor

      Tinnitus Since:
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      Otonomy issued a press release this morning on a number of presentations that they're giving at the upcoming Neuroscience 2021 meeting. These two caught my eye:
      • “Local delivery of BDNF (OTO-413) and a selective TrkB agonist (M3) restores hearing function in models of cochlear synaptopathy” by Fernandez et al.
      • “Novel fab fragments derived from Trk-selective agonist monoclonal antibodies are potent and selective antagonists of the TrkB and TrkC receptors” by Siegel et al
      Anyone know what these mean? They're giving a separate presentation on OTO-413, and I don't think OTO-413 contains a selective TrkB agonist. Could this be a new formulation that they're working on that's more potent? Or is this somehow related to what they've already done?
       
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    13. Tau
      Probing

      Tau Member

      Location:
      Europe
      Tinnitus Since:
      2019
      Cause of Tinnitus:
      2019-Concert, 2021-headphones/acoustic trauma at 110dB,16kHz
      Probably a pre-clinical study on mice or rats.
       
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    14. patorjk
      No Mood

      patorjk Member Benefactor

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      The more I dig into this, the more it does look to me like follow-on pre-clinical work for an improved OTO-413 - though probably something in the early stages. TrkB agonists seem to help BDNF.

      Fernandez was a previous co-author on some of their previous BDNF studies. I can't really see any reason for them to do these presentations unless they're working on an improvement of some sort - though maybe I'm seeing what I want to see? I guess we'll find out soon enough though.
       
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    15. Joeseph Stope
      Innocent

      Joeseph Stope Member

      Tinnitus Since:
      1992
      Cause of Tinnitus:
      noise? infection? negative stress? other?
      Just for your interest @patorjk, as you are knowledgeable in corporate matters and that is a a useful background to have {but most people here shouldn't go paddling in shark-infested waters}.

      Auris Medical seem to have changed their name to Altamira Therapeutics but still have the web address as aurismedical.com. Just sayin' like Not much moving there except their stock price on the six month interval, but it's up overall on the year. But then the other hearing research stock seem to be facing headwinds too.
       
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    16. patorjk
      No Mood

      patorjk Member Benefactor

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      Otonomy has released its Q3 financial results. Most interesting updates:
      • OTO-413 study is ahead of schedule and results are now expected in early Q2 of 2022.
      • The expanded OTO-413 study is now being called a "Phase 2a" study in their press releases.
      • They're adding a "full dose" cohort to the expanded study. It'll be a higher dose than they've tested before. They didn't say how big this dose would be (at least I didn't catch anything related to it). This new cohort will consist of 12 additional patients (8 getting the drug, 4 getting placebo).
      • They expect to start a Phase 2b study for OTO-413 using the full dose version by the end of 2022 (assuming favorable results to the current Phase 2a study).
      • Nothing was said about the 2 presentations I mentioned above. I'm guessing the science is too early to be of interest to investors, at least at this point.
       
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    17. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
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      Good news on the OTO-413 front; and encouraging to see them ahead of schedule.

      As far as the addition of the TrkB antagonist study, I suspect that would need to be a separate round of trials. So, they may not be ready to comment until the outcome for OTO-413 is much more clear (IE: Clearly targeted patient population, appropriate primary outcomes, stat sig patient outcomes).
       
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    18. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      It looks like the summer of 2022 is when we will have the results to all of these studies; PIPE-505, FX-322 severe trial and now OTO-413. I don't know how much longer I can wait. Every day just drags on, knowing we might be so close to a cure.
       
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    19. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

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      Great to hear about OTO-413. I thought the repeat trial with higher dosage was Phase 1b but I’m glad they are calling it Phase 2a. Still a bit sad they delayed OTO-413 but at least Phase 2b will start end of next year so it would a year or two behind FX-322.
       
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    20. EkkoMusic

      EkkoMusic Member

      Tinnitus Since:
      01/2021
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      I hope it’s good news too, but I assume that the “full dose” trial is also due to early data suggesting that a stronger dose would yield better results. I wonder what results they were (or weren’t) getting that inspired this adjustment.

      That said, I do not know how much data they would have so far. I am also purely just speculating and reading into the news—I hope everything is looking promising and it’s always great seeing the wheels in motion.
       
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    21. patorjk
      No Mood

      patorjk Member Benefactor

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      The Q3 call and press release were very strange, they didn't address the name change at all. Even the clinical trials page still has it listed as Phase I/II. Apparently the reason they're so ahead of schedule is because they're receiving a high demand for OTO-413 from their clinical sites, which recruit using existing patients (i.e. patients that have been seeing doctors for quiet some time regarding their hearing loss). To me this could indicate that OTO-413 works, as maybe word has gotten around and that's why so many are signing up?

      I'm glad they upped the dose too, I was surprised they didn't do that when they announced the expanded trial. Apparently they had to get permission from the FDA - my gut assumption is that that just took forever and it's why they're only tacking that on now near the end of the trial. It should give the trial a much better chance of success though, as they said that the 0.3mg dose cohort (the highest dose cohort of the original study) showed the most improvement and that dosing seemed to impact results. I actually think their Otividex drug failed due to being under dosed.
       
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    22. Nobody19

      Nobody19 Member Benefactor

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      Am I only one who thinks it's awesome both Otonomy and Frequency Therapeutics are already working on improved versions of their drugs? Progress in the field seems to be quite steady.

      Things might improve even faster once these companies get cash from a released drug (a darn shame that their Meniere's trial was a failure!)
       
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    23. patorjk
      No Mood

      patorjk Member Benefactor

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      I decided to contact Otonomy about the Select TrkB Agonist talk and they sent me the slides - they're attached to this post. I was wrong in my assumption that it was for a next-generation OTO-413. Instead it's related to the preclinical work for OTO-413 and how they tested 2 drugs for possible advancement (BDNF and M3). The IR person told me that they have IP covering M3 and could develop the molecule in the future if appropriate.

      I'm a little bummed, as I was hoping this was hinting at something exciting on the horizon, but I suppose if OTO-413 is a success this coming Spring they'll be looking into ways to improve it anyway. I also wonder if I gave them any ideas with my questions, as maybe mixing the two would have a synergist effect.
       

      Attached Files:

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    24. Trevor_phillips

      Trevor_phillips Member

      Tinnitus Since:
      2019
      Cause of Tinnitus:
      NIHL
      They're talking about improvement when the subject gets injected OTO-413 the day following the noise trauma. So it doesn't work for people who got noise trauma years ago?
       
    25. aorelia

      aorelia Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Headphones
      Is there a timeframe for when OTO-413 can be used? It looks like they tested immediately after noise trauma and 7 days after.
       
    26. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

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      The subjects are rats.
       
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    27. Trevor_phillips

      Trevor_phillips Member

      Tinnitus Since:
      2019
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      NIHL
      Oops, I forgot that spiral ganglion neurons remain active for decades in humans, so the synapse regeneration is possible whatever the date the noise trauma occured.
       
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    28. Philip83
      Jaded

      Philip83 Member Podcast Patron Benefactor

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      Can't wait until the singularity occurs and we can hand this over to an AI and have it solved in 5 minutes.
       
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    29. aorelia

      aorelia Member

      Tinnitus Since:
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      I wonder if this can be measured somehow with someone's tinnitus. Like would the change of tone/pitch/loudness differ?
       
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    30. Chandler

      Chandler Member

      Location:
      İstanbul
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      I have had hearing loss in fine sounds since I was a child. Is there any chance that OTO-413 will help? Does it eliminate the use of hearing aids?
       
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