Frequency Therapeutics — Hearing Loss Regeneration

Discussion in 'Research News' started by RB2014, Dec 8, 2016.

    1. AUTHOR
      AUTHOR
      RB2014
      Confused

      RB2014 Member Benefactor

      Location:
      US
      Tinnitus Since:
      12/2014 became noticable
      Cause of Tinnitus:
      Loss of hearing and then stress and anxiety
      At this point we will have to wait and see what the additional trials tell us. My only point was that FX-322 was created to cure hearing loss... not increase word recognition scores. Debating on which one is more important is not going to help any of us. If the additional increased word scores hold true for subsequent trials, then this is an unexpected win for them and hopefully they can build off that. At the end of the day, as everyone has pointed out, there are still many things they don't understand about the human ear and hopefully with additional testing they can figure out how to make FX-322 more effective.
       
    2. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      I love how a 1920s test is somehow the gold standard of hearing, and real life changes are "illusions."
       
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    3. AUTHOR
      AUTHOR
      RB2014
      Confused

      RB2014 Member Benefactor

      Location:
      US
      Tinnitus Since:
      12/2014 became noticable
      Cause of Tinnitus:
      Loss of hearing and then stress and anxiety
      And... From what we think... There should have been improvements in the 8 kHz to 16 kHz range as well, since FX-322 would have hit those areas first, which would have only helped with the word scores.

      Word scores also dropped in the 1 to 2 year time period... I wonder if any improvements in the 8 kHz to 16 kHz range didn't stand the test of time as people seem to lose those frequencies faster for some reason.
       
    4. 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
      To be honest, you're treading on unrealistic expectations territory with this comment.

      How do we define any drug as a bonafide CURE for hearing loss, and associated symptoms (tinnitus, hyperacusis, distortions, et al)? FX-322 cannot simply be a CURE for hearing loss by itself, because it's been known from very early on (as early as 2018) that it cannot repair areas of the cochlea where the synaptopathy is present with otherwise healthy hair cells. So, in any individual, where hearing loss is likely a mixed pathology (dead cells + synaptopathy), it may only be able to resolve part of the underlying condition leading to hearing loss. Therefore, FX-322 ALONE can never be a full hearing loss cure. It can only partially treat a specific underlying issue.

      To get even more philosophical on you, how do we define a CURE for hearing loss? Is one cured when their hearing is fully restored back to the day they shot out of mom's uterus? Or just when they're able to ACE the three standard hearing loss tests (Audiogram, WR, WIN)? Or does the CURE mean that they no longer experience tinnitus at all? Is that possible? Some have provided old research that shows that people with "normal" hearing still experience tinnitus when things get uber quiet. So, what's the cure benchmark there? How about hyperacusis? Or, is the CURE when someone's quality of life gets above a certain "normal" threshold?

      This is why Frequency Therapeutics uses the term, "Disease Modifying Effect"... FX-322 is a treatment for those with SNHL/NIHL where hair cell death/damage has occurred. It has been demonstrated in vitro that FX-322 is restoring lost hearing by replacing those poorly performing/missing cells. This is also believed to be happening in vivo, and has been observed by those clinical measurement improvements. Even though the patient saw a benefit from specific hair cells being restore anew, neighboring hair cells and those untouched by FX-322 may still be at their aged/worn state, or have some form of synaptopathy. Therefore, FX-322 can only modify their hearing loss disease so much, but not likely to a NEW state. It's also been shown that the progression of hearing loss in those that received FX-322 still realized ongoing deterioration in their hearing after initial restoration. This is what should be expected when the progression of a disease is modified by drug intervention. A patient gets X% better, rolling back their progression a few years, but eventually they return the original baseline without regular intervention. A perfect example is the long-term study on those Phase 1/2 patients.

      Screen Shot 2021-04-14 at 5.02.11 PM.png

      As for measuring hearing loss:

      Audiogram, Word Recognition, Word in Noise are the three COMMON assessments used in clinical practice to determine a patient's level or hearing loss. These three are generally accepted as the "standard" for hearing treatment practice across the United States. Even researchers and clinicians agree these tests are imperfect, not sensitive enough for specific conditions, and do not provide a complete picture of a patient's hearing condition. Yet, FX-322 has shown improvement, although not consistent, on all three tests.
       
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    5. Trevor_phillips

      Trevor_phillips Member

      Tinnitus Since:
      2019
      Cause of Tinnitus:
      NIHL
      If I take the example of a teacher explaining a lesson to his students in a large auditorium, assuming that all students have excellent hearing, the teacher will still need a microphone to properly interact with the whole room.

      This is what I want to explain. A minimum amount of amplification is fundamental even if the mechanical-electrical transduction triggered by the inner hair cells is very good. Students basically won't understand anything even if they have inner ear hair cells in good health.

      So, based on the fact that hearing loss is mostly about destroyed outer hair cells and inner hair cells as well, one cannot be able to figure out something without an minimal improvement at sound amplification. In addition to, it is known that outer hair cells have the role of filter, they allow (with synapses) to indirectly understand speech in noisy environments.

      This is the reason why hearing aids are limited in noisy environment, because OHCs are damaged and they perceive upcoming sounds as an hubbub, despite good inner hair cells condition.

      For OTO-6XX, it is known that Otonomy is using a gel (for instance like the one used in OTO-413/OTO-313) that can be long lasting, so the effect could be very sustainable and could reach the cochlea from the apex to the base.

      For the rest, I'm basing my speech on the currents pre-clinical tests that they're doing currently (they said indirectly that they're pleased with what they're seeing) and the picture reconstruction, with hair cells marked in green. We don't have any picture of FX-322 regrowing hair cells and the one used by Frequency Therapeutics is from Novartis.
       
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    6. Kleiner

      Kleiner Member

      Tinnitus Since:
      08/2020
      Cause of Tinnitus:
      Sound trauma
      Just my opinion:

      FX-322 in the upcoming results must show clinically significant results in WR and extended audiogram tests, even if they are minimal, they must prove that the drug works.

      WR tests measure IHC but also OHC, the two are inseparable.

      The theory that FX-322 already repairs IHCs and then OHCs is limited, some patients have damaged OHCs and almost no IHC damage.

      The only explanation would be that OHCs cannot grow back unlike IHCs, but it will take clear results on WR tests to prove it.

      Their biggest mistake is not adding objective tests like OHC emissions

      With the two studies of Phase 1b and Phase 2a, I think we will have enough evidence to declare the FX-322 as working or not.

      We don't have enough information to form a solid opinion, positive or negative.
       
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    7. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      Do we know when Otonomy is going to start clinical trials for OTO-6XX? I haven't seen anything from them.
       
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    8. Trevor_phillips

      Trevor_phillips Member

      Tinnitus Since:
      2019
      Cause of Tinnitus:
      NIHL
      Absolutely nothing is known about OTO-6XX. They did say that they are going to claim any information when they'll have an update to provide about the current pre-clinical tests. I won't be surprised if this is after OTO-413 results in mid-2022. I think that OTO-6XX will move to clinical trials when Otonomy will have enough cash, after the next phases of OTO-413/OTO-313.
       
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    9. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      Some users will shoot me dead, but I consider the current formulation of FX-322 to be like an attempt at a small cure. I think the difference between a treatment and cure is that a treatment is intended on covering up a problem.

      Now of course, a great treatment can actually be better than a small cure. For example, Ebselen, as a potential treatment for inflammation and NMDA excitability, could be a great treatment. Prednisone can be a great treatment.

      Growing hair cells is a cure. It doesn't cure all of hearing loss, but it's a real attempt at a cure. Most people with chronic illness know the difference.
       
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    10. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      I didn't realize it's also an NDMA antagonist. That's great! Its the same stuff as OTO-313
       
    11. 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
      I'd meet you halfway and agree to that term, "Small Cure" ... since it really only fixes one of the many underlying causes of SNHL.
       
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    12. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

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

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
    14. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

      Location:
      Clown World
      Tinnitus Since:
      -
      Cause of Tinnitus:
      -
      I know, but I thought the reason why his tinnitus might have come back was because he was exposing himself to loud noise.
       
    15. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      That's the hope and there is definitely good potential with the drug. I think some people will have a greater response than others, though.
       
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    16. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      So when's the next big date on results for FX-322?
       
    17. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      Sometime in Q3, probably June-August.
       
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    18. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      Probably late Q2: ARHL and Severe arms.
       
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    19. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      Supposedly in June.
       
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    20. Chad Lawton

      Chad Lawton Member

      Tinnitus Since:
      2/19/18
      Cause of Tinnitus:
      Possible Ototoxicity + Noise Exposure
      Of those that improved in the Phase 1/2 trial, their WR scores were on average 25 or less out of 50. That means they can only hear half the words in a conversation or less. It's absolutely life changing to go from understanding only 1 out of every 3 words in a conversation to hearing 2 out of every 3 words.
       
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    21. d'Wooluf

      d'Wooluf Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      unknown
      I was hoping for both but I broadly agree with you. It was such a smooth change of emphasis we pretty much all bought it. I was hoping to throw away my hearing aids. But if FX-322 or some other treatment doubled my WR scores, that would still make a huge difference to my life.
       
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    22. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Does anyone care about tinnitus anymore?
       
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    23. AUTHOR
      AUTHOR
      RB2014
      Confused

      RB2014 Member Benefactor

      Location:
      US
      Tinnitus Since:
      12/2014 became noticable
      Cause of Tinnitus:
      Loss of hearing and then stress and anxiety
      If FX-322 can restore hearing 8 kHz and up, there is a good chance this could help people with high frequency tinnitus. We are just waiting for more results to come out.
       
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    24. AUTHOR
      AUTHOR
      RB2014
      Confused

      RB2014 Member Benefactor

      Location:
      US
      Tinnitus Since:
      12/2014 became noticable
      Cause of Tinnitus:
      Loss of hearing and then stress and anxiety
      Agreed. When this whole thing started, I was hoping to throw away my hearing aids as well. At this point it looks like we might get some hearing back in the 8 kHz range, get better word scores and keep our hearing aids. I am ok with that.
       
    25. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      Yes. We just recognize that it's an ugly path forward with incremental progress. Trust me, I know all about long-haul thinking. My reason for following FX-322 is that I want it to succeed so that their nerve regeneration drug has a better chance. This is a decade+ long vision. It sucks, but it's reality, whether we accept it or not.

      And BTW, there really are some promising treatments for tinnitus.

      upload_2021-4-29_10-51-11.png
       
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    26. Guywithapug
      Dreaming

      Guywithapug Member

      Location:
      USA
      Tinnitus Since:
      October 2020
      Cause of Tinnitus:
      SSHL
      Yes, I would like to know more about the quality of the restoration. Metrics of how far up beyond 8 kHz and to what degree in terms of dB gain. Was there significant tinnitus relief? Also, what is the longevity of said restoration?
       
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    27. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      6B78D0D6-755B-4330-9728-657EB779A538.gif
       
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    28. Bill Arsenault

      Bill Arsenault Member

      Location:
      Boston.
      Tinnitus Since:
      Permanent and intrusive since 2017.
      Cause of Tinnitus:
      Medication / Noise Over Exposure
      Ever having any choice again whatsoever is so 2019.
       
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    29. 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
      Now that the multi-dose door is closed for the foreseeable future, I wonder if they are considering a trial where both ears are given a single dose?
       
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    30. Lurius
      Wishful

      Lurius Member

      Location:
      Oslo, Norway
      Tinnitus Since:
      September 2018
      Cause of Tinnitus:
      Valsalva maneuver
      What about 6 kHz? Any hope for people with hearing loss in that range?
       
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