Frequency Therapeutics — Hearing Loss Regeneration

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

  1. Watch Hazel share good news about tinnitus
    1. kiki

      kiki Member Benefactor

      Tinnitus Since:
      10/2015
      Cause of Tinnitus:
      noise
      I heard they seemed to say in the webinar that there was no improvement in EHFPTA in Phase 2.

      Do you think this means "compared to a placebo"?

      Do you think EXFPTA had the same problems as word recognition?

      I think a cheat that doesn't hear a beep is easier than a cheat that doesn't understand a word.
       
    2. Artem
      Frustrated

      Artem Member Benefactor

      Tinnitus Since:
      10/2021
      Cause of Tinnitus:
      vaccine + acoustic trauma
      The audiogram can be extended (up to 16 kHz inclusive). In rare cases, a person's speech captures 8 kHz. If the drug does not reach the appropriate depth, then where do the changes in word perception come from?

      To the Question of the honesty of the subjects - you can give a combination of short and long signals.

      P.S. I don't quite share this analogy with a damaged audio system and an increase in volume. I think the analogy with adjusting frequencies with an equalizer is more appropriate.

      Best regards,
      Artem
       
    3. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      Can someone answer me this: if I am ineligible to be in their trial due to having too good word scores, does that mean I'll have to wait until it's released to the open market, or would I still be ineligible?
       
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    4. SD7
      Angry

      SD7 Member

      Tinnitus Since:
      Mid /June 2021
      Cause of Tinnitus:
      Vaccine + Noise
      The delivery critique is well warranted and they are working on it in the reformulation of FX-322 and the upcoming FX-345. It's not as rare as you may think, f, s and t can breach that upper bound depending on the pitch of the speaker.

      You're right there are most sophisticated ways to perform audiograms, however audiograms are primarily testing the outer hair cells whereas frequency is primarily interested in regenerating the inner hair cells for clarity.

      I think the aforementioned analogy is fine if you consider the difference purposes the hair cells have. Outer hair cells amplify sounds and can be tested via the audiogram whereas the inner hair cells are for clarity and can be tested via word scores or word in noise tests. @Chad Lawton is right if you had to choose between clarity and loudness you should almost always prefer an increase in clarity. Hearing aids can help with subsets of outer hair cell dysfunction however there is no equivalent for clarity.
       
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    5. Artem
      Frustrated

      Artem Member Benefactor

      Tinnitus Since:
      10/2021
      Cause of Tinnitus:
      vaccine + acoustic trauma
      Hmm, I'm sorry. I believed that the outer sensory cells are responsible for high tones, and the inner ones for low tones. The audiogram can cover the entire hearing range from 100 Hz to 20 kHz. But it looks like it’s not so... Strange, but very interesting...

      Anyway, thanks for the clarification and optimism.

      Веst regards,
      Artem
       
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    6. DimLeb

      DimLeb Member

      Tinnitus Since:
      14/03/2021
      Cause of Tinnitus:
      Idiopathic Cochleopathy Or Maybe Loud Music
      @Artem, "the inner hair cells convert sound vibrations from the fluid in the cochlea into electrical signals that are then transmitted via the auditory nerve to the brain whereas the outer hair cells amplify low-level sounds that enter into the fluids of the cochlea".

      So for each frequency, low or high (20 Hz - 20 kHz), I imagine it's both the two layers (inner and outer hair cells) that are responsible to pick it up.
       
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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
      Does FX-322 regrow both inner and outer hair cells, or just inner? What if you have outer hair cell damage, but not inner? Would this drug still work for you?
       
      • Good Question Good Question x 1
    8. Akk

      Akk Member Benefactor

      Location:
      Finland
      Tinnitus Since:
      2006
      Cause of Tinnitus:
      Unkonown
      To clarify, outer and inner hairs cells are paraller in ”tube”. First cells, near ear drum, react to high frequencies and more deeper you go more lower frequencies cells react there.

      https://basicmedicalkey.com/special-senses-2/
       
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    9. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      Their exclusion criteria makes my head hurt. If you have mild to moderate hearing loss, FX-322 should be able to use your progenitor cells to regrow completely new hair cells, theoretically restoring hearing. I noticed on their exclusion criteria, they list:

      "Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10dB at two or more contiguous octave frequencies in the study ear."

      But, what if your hearing loss is sudden sensorineural due to loud music? That's not conductive, right? So, you should be good to go. Can someone look at my audiogram and tell me what's what?

      Scan_0001.jpg
       
    10. SD7
      Angry

      SD7 Member

      Tinnitus Since:
      Mid /June 2021
      Cause of Tinnitus:
      Vaccine + Noise
      Theoretically both, however practically it heavily prefers the inner hair cells.
       
    11. ColinUK

      ColinUK Member

      Tinnitus Since:
      2013 initial, worsened 2020
      Cause of Tinnitus:
      Initial Music Gig, Worsened Cinema or possible covid
      With all these additional trials has there been any mention of tinnitus at all. Before with the first trial with just a handful of people they said that they had some anecdotal reports of tinnitus improvement. Now after all these trials with hundreds of patients and where they actually opted to test for tinnitus improvement there has been no updates. Or did I miss them?

      I mean in light of the poorer than expected hearing signal improvements you would think they would be shouting from the rooftops if there had been improvement of people's tinnitus.

      So I can only assume for tinnitus it's a total dud? Or did I miss something?
       
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    12. 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
      They're still testing tinnitus outcomes using the TFI in Phase 2B.

      However, at this point, with the FDA giving them a clear path to approval with word score / speech recognition measures, I don't see why they'd bother mentioning tinnitus.
       
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    13. ColinUK

      ColinUK Member

      Tinnitus Since:
      2013 initial, worsened 2020
      Cause of Tinnitus:
      Initial Music Gig, Worsened Cinema or possible covid
      But surely an improvement in tinnitus would be proof that something positive is happening in the ear. I mean if someone said after their injection they had a 3 dBa improvement and an elimination of tinnitus I would be more impressed with the elimination of tinnitus.

      I think the only reason to omit it is if no one is reporting any positive affect? Which unfortunately sucks.
       
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    14. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Ya, they would have reported improvement in tinnitus if it happened. They needed some more good news.
       
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    15. 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
      They have to see statistically significant improvements in the TFI from the participant's baseline. I highly doubt that the Severe group (assuming considering the 3 dB SIN reference) would see tinnitus improvement if they didn't see significant word score improvement. It's also a problem of getting enough participants that have tinnitus to be significant. Some do have it, some do not.

      Given how heterogeneous tinnitus is "experienced" on top of how heterogeneous acquired SNHL hearing loss is, it's likely that greater coverage of the cochlea may should better results for tinnitus improvement from baseline (FX-345).
       
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    16. Survivor234
      Hurting

      Survivor234 Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Noise-induced/Headphones
      I have a question. Why are they focusing on word score/speech recognition and not high frequency hearing? Wouldn't the latter be more indicative of any sort of successful hair cell regeneration?

      I have a feeling that regenerating hair cells, and by extension eliminating tinnitus, is probably going to be a multi-treatment process. I feel like we lose more than we gain from the competitiveness and the close-guarding of advancements and information among firms.

      Hopefully, once the treatments are on the market, the curtain will rise and people will begin to experiment with different treatments (I know for certain that tinnitus sufferers will take as much treatments as they can).
       
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    17. 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
      Their strategy has shifted to focus on it.

      1. FX-322 has shown the most statistically significant improvements in word score / speech recognition amongst trial participants.
      2. There is data available on patients with word score / speech recognition deficits, making recruiting more accessible in a reasonable timeframe in the US. HF audiograms for patients are not common at all in the US.
      3. The FDA gave Frequency Therapeutics the "all clear" to focus on word score / speech recognition as an acceptable outcome for FX-322. So, why bother deviating?
       
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    18. Survivor234
      Hurting

      Survivor234 Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Noise-induced/Headphones
      But why isn't there a statistically significant improvement in high frequency hearing?
       
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    19. 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
      One can only speculate.
       
      • Agree Agree x 1
    20. ColinUK

      ColinUK Member

      Tinnitus Since:
      2013 initial, worsened 2020
      Cause of Tinnitus:
      Initial Music Gig, Worsened Cinema or possible covid
      From the Tinnitus Talk Podcast interview eons ago:

      "Carl: Again, we don’t have data. Certainly there is anecdotal reports as patients have come back and visited with ENTs when they have had conversations with them about how they are doing. Some of them have offered that they have had improvements in tinnitus"​

      Makes no sense why they would keep it secret. Their first trial with a handful of patients they were happy to report it. Why after 100s injected have none come forward to report an improvement and if they had, why on earth would Frequency Therapeutics, who so happily told us the anecdotes before, not mention anything. What possible advantage could there be to not report people's perception of their tinnitus having improved?

      I mean, if they found out it only gave a small hearing boost but fixed tinnitus, I think they would be happy to get the drug approved as a tinnitus drug?
       
      • Agree Agree x 3
    21. kiki

      kiki Member Benefactor

      Tinnitus Since:
      10/2015
      Cause of Tinnitus:
      noise
      I think this is because in Phase2a, there was an improvement in the placebo group that canceled out the significant improvement.
       
    22. Survivor234
      Hurting

      Survivor234 Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Noise-induced/Headphones
      Do you have any evidence of this? Are the Phase 2a results publicly available anywhere to see?
       
    23. 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
      They aren't keeping it a secret.

      The first trial had anecdotes, but no data to validate improvement from placebo. No TFI.

      In the phases that followed, TFI was added was a secondary outcome. Phase 2A data was effectively worthless and inconclusive, so no way to know if TFI data showed improvements. The other two placebo-controlled Phase 1Bs (Age-Related, Severe), weren't effective at the primary outcomes, so it's highly likely that TFI as an experimental outcome didn't provide significant data either.

      There may be a patient or two that did have an improvement in their tinnitus, but now that their data is aggregated with a pool of 100s, it's probably not significant at a group-level. EX: Tinnitus = YES. Therefore, they can't reasonably say, "hey a couple people's tinnitus got better, but it's all anecdotes." That would only introduce unnecessary scrutiny, and take focus off of where the drug IS showing an effect.
       
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    24. 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
      It's in their investor deck, and they do a video of it on the R&D day page. On their website.
       
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    25. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      C'mon man! I had a lot of faith in this drug too but obviously there was no improvement in tinnitus. Faking word scores wouldn’t mess up the TFI data.
       
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    26. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

      Location:
      Prison
      Tinnitus Since:
      -
      Cause of Tinnitus:
      -
      If you’re talking about audiograms in the Phase 1b trials, there were a few patients that had an improvement at the highest frequency which was tested at 8 kHz.

      Now with Phase 2b trial they are testing up to 16 kHz so we should see more patients with an improvement in audiograms.
       
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    27. 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
      If you choose to go into a trial and fake word scores, who’s to say you wouldn’t underweight other data?
       
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    28. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Are you saying they inflated their TFI?
       
      • Good Question Good Question x 1
    29. SD7
      Angry

      SD7 Member

      Tinnitus Since:
      Mid /June 2021
      Cause of Tinnitus:
      Vaccine + Noise
      I think Diesel's point is that it's tainted regardless.
       
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    30. Survivor234
      Hurting

      Survivor234 Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Noise-induced/Headphones
      So, was the lack of improvement because patients could already hear at 8 kHz or were the patients incapable of hearing at 8 kHz and there was no improvement?

      Furthermore, if they could already hear at 8 kHz, how did they get any improvement?

      Hopefully it's the former but your phrasing allows for the latter meaning.

      Also, isn't FX-322 done with Phase 2 by this point? Is Phase 2b new or a redo?
       
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