Otonomy OTO-313 — Treatment of Tinnitus

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

    1. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

      Location:
      Clown World
      Tinnitus Since:
      -
      Cause of Tinnitus:
      -
      If FX-322 does not get rid of your tinnitus completely, then you may need something like OTO-313 to permanently get rid of it.
       
      • Agree Agree x 1
    2. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Correct me if I'm wrong but doesn't this one have a very good chance of approval?

      They don't need to regenerate anything, they just need to prove it relieves tinnitus above placebo.
       
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    3. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Seems like it but a similar drug, AM-101, with the same mechanism of action failed.

      Going by AM-101's ClinicalTrials page, they were much less selective about their participants/time frame.

      Otonomy need to pick the right patient for this (and the right patient needs to apply) but they have the advantage of learning from Auris Medical's failure.
       
    4. kingsfan
      Mellow

      kingsfan Member

      Location:
      Southern California
      Tinnitus Since:
      Sep 17 '20 / Oct 20 '20 / Mar 31 '21
      Cause of Tinnitus:
      turning everything up to 11
      I’ve read the same about Ketamine - the worse the tinnitus, the better it may work.
       
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    5. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      It's possible but Ketamine also acts on central NMDA receptors so it has even more variables. Some people do worsen on Ketamine and I wonder if it's because they get more cochlear blockage and their problem is more central (so you are reducing peripheral excitation but maybe temporarily reducing the overall auditory signal centrally).

      I have only ever read Ketamine worsening being temporary, though, with short term use anyway, so that's good.
       
    6. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Good thing Otonomy is being very selective. Did AM-101 trials do as well as OTO-313 trials have?
       
    7. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
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    8. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Do you know why? Auris Medical states on their website that they are still working on it.
       
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    9. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Do I know why they didn't meet their end points? No, not sure.

      I also just read this paper (didn't realize the full paper was free). Phase 2 had some interesting findings. The idiopathic hearing loss group didn't respond but the acute noise (within 3 months) and post otitis media group did. Seemed to work better in unilateral cases, too. They made the case for some types having more local NMDA receptor hyperexcitabilty than others.

      One puzzling finding is that the MML did not change even when improvements were seen. They even speculates that the more "objective" measures of tinnitus don't seem to correspond with the subjective findings of improvement (they weren't suggesting it was psychological but questioned how useful MML was here).

      I did also notice that their improvements took time (over a week), so I have to wonder if Otonomy's gel is a huge advantage here. Seems like extended release is the best strategy for IT injections, period.

      Otonomy's exclusion criteria also states:

      "temporomandibular joint disease (TMJ) associated with tinnitus perception"

      Which makes me wonder if they suspect it doesn't work as well in somatic cases and Auris Medical may not have accounted for that?

      Tl;dr: treating the cochlear NMDA receptor is complicated and they need to pick the right patients.
       
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    10. Pero1234

      Pero1234 Member

      Tinnitus Since:
      02/2018
      Cause of Tinnitus:
      home theatre system + high pressure washer
      I received this email from Otonomy this morning:

      Otonomy Announces Closing of Public Offering and Full Exercise of Underwriters’ Option to Purchase Additional Shares

      What does this mean?
       
    11. GBB

      GBB Member Hall of Fame

      Location:
      NYC
      Tinnitus Since:
      2016-2019 (Mild, Cured) 8/2020 (Severe)
      Cause of Tinnitus:
      Virus / Microsuction / Acoustic Trauma
      Sounds like they did a follow-on offering to raise more money by offering additional shares to the public, though I didn't read beyond what you wrote (e.g. did not google it). It's not unusual for a company to either issue debt or additional shares to raise funding, though it sucks for existing shareholders whose shares are diluted in value.
       
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    12. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      As a side note, Gacyclidine, the molecule in OTO-313, is similar to Ketamine.
       
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    13. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      I don't think anyone has posted this video yet but this is pretty interesting (you can use any name/company and email to sign up):

      https://wsw.com/webcast/needham107/otic/2250710

      Some things to note:
      • They have enough funding until Mid-2023 apparently
      • Q2 2021: Initiate OTO-413 Expansion Study
      • Mid-2021: OTO-825 Program Update (Congenital Hearing Loss)
      • Mid-2022: OTO-313 Phase 2 Results
      • Mid-2022: OTO-413 Expansion Study Results
      They also talked about how their drug differs from AM-101 at the end, and how their drug is more specific. And how their trial design differs from other companies because they will not make the same errors other companies have.
       
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    14. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Does the 2023 date take into account the recent sale of shares that @Pero1234 talked about?
       
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    15. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      So I am not really well versed with the implications of your question, but one thing I can say is the video I linked took place on the 13th of April and the share thing happened earlier today. Hopefully someone else can answer your question but based on the video they emphasized that they have a good amount of funding and that the trials should go through no problem.
       
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    16. AfroSnowman
      Balanced

      AfroSnowman Member Podcast Patron Benefactor

      Tinnitus Since:
      April 16 2019
      Cause of Tinnitus:
      Nonnatural energy source
      What is an ‘expansion study’?
       
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    17. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      My ears are too sensitive to listen right now. Do you remember what they said about how their trial design differs?
       
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    18. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      So Frequency Therapeutics is sitting on some $200M, how much does Otonomy have?
       
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    19. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      Sorry for the late response. I am going to basically paraphrase what Dave Weber said in the video. I think there is a lot of technical stuff throughout the whole video that you can probably understand better than me. If you can manage to watch it yourself there is a lot of juicy stuff after 30 minutes in. In the beginning he talks about OTO-313, then talks about the other products in Otonomy's pipeline.

      So let's get started:
      • He talked about how his team thought the mechanism of action used in other previous tinnitus trials wasn't really applicable. I believe he directly called out Auris Medical when he talked about another company that previously tried using an NMDA receptor antagonist.
      • He said OTO-313's formulation is very valuable, from a single administration it shows prolonged results compared to what others have tried from multiple injections. He said the issue with multiple injections is that you don't really get sustained concentration at a high level, and that you cannot "drive" a drug through the ear.
      • He emphasized trial design, and how the lead-in will be rigorous for this trial. He talked about how in previous trials (I believe he was talking about AM-101) there was no consistency in the level of tinnitus people had, so the minimum level of tinnitus varied a lot. He said that there were people with mild tinnitus in the trial, and that he wouldn't expect to see those people improve anyway. He also thinks there were issues with how people were followed after the trial. He said OTO-313's trial is different from this because he wants to ensure stability of disease and a strong lead in phase along with rigorous follow up. He emphasized that he thinks the trial design for OTO-313 and OTO-413 is very strong.
      • Phase 3 OTIVDEX data was mentioned, they are analyzing what occurred in the trial. They are trying to understand if anything went wrong and if it did go wrong, there MAY be discussion with the FDA about what happened. The results of the analysis will come out within the next two months. They will see what they can find, and he said he does not think they will pursue more clinical trials on OTIVIDEX but again they are looking through all the data across all trials to see what happened and if anything significant is there there may be discussion with the FDA.
       
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    20. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      So I am not entirely sure what it is either, but I did a little bit of googling so I am going to try my best to answer this, hopefully someone else can chime in as well. Here's what I found: "These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD), and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is collected".

      So I assuming they are going to enroll more patients with different eligibility criteria than the other studies, to further see how the drug is tolerated or how it works against different populations. Again, I am not 100% on this so hopefully someone else can chime in if I am wrong.
       
    21. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      So I am not really good with knowing how companies operate and stuff but I think I have a rough idea of what's going on here. I believe they had $86 million in cash on hand, then earlier this month they secured another $30 million in financing, and I think another $15 million on top of that?

      In the video he states:

      "We have the runway to get not only past the mid 2022 readouts for OTO-313 and OTO-413, but well into 2023, there is no financing overhang here, we have the cash to run our programs and advances those programs clinically as well as the other programs discussed"

      Here is a screenshot I pulled from the video:

      Screenshot 2021-04-20 194355.jpg
       
    22. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      @Frequency Therapeutics.

      There are now 2 Pharmaceutical Companies that have identified multiple injections as detrimental to the therapy itself.

      @FGG, @Diesel, what do you make of this?
       
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    23. r34d1ng

      r34d1ng Member

      Tinnitus Since:
      Unknown
      Cause of Tinnitus:
      Unknown
      Shots fired :whistle:
       
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    24. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      Definitely a call out to Frequency Therapeutics.
       
    25. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      Armchair quarterbacking.
       
    26. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Well, Otonomy is going for the extended release approach and so far so good.
       
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    27. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      Okay, so I was thinking about OTO-313 and then I realized that OTO-313 isn't really a cure, it seems like it mostly just improves symptoms for people by reducing their TFI score.

      As far as I know there hasn't been a total remission of tinnitus for those who have received OTO-313.

      I believe it mostly just reduces the severity of tinnitus or it just reduces the volume of it.

      What do you guys think?
       
    28. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      There has not been a total remission in anyone treated with OTO-313 so far. It reduces severity and volume in 43% of those given the drug, in 29% of those given the drug it reduced TFI by 20 or more points. The loudness and annoyance charts matched pretty closely.
       
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    29. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      It could still help us very very much, even if not a cure, if it reduces the intensity/severity, we could cope better.
       
      • Agree Agree x 5
    30. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      I wish OTO-313 could lead to total remission. Well, I'll take whatever I can get. Any improvement is better than nothing. I wonder as more time goes on after receiving OTO-313 if it would lead to further improvement or return to baseline. I'm just glad that there is some success at least.
       
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