Frequency Therapeutics — Hearing Loss Regeneration

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

    1. Gorbeh3

      Gorbeh3 Member

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Hearing Loss
      Clinical Study Sites
      New York, New York
      New York, New York (Actually NJ)
      Albany, New York
      Amherst, New York
      Richmond, Virginia
      Norfolk, Virginia
      Winston Salem, North Carolina
      Novi, Michigan
      Cincinnati, Ohio
      Orangeburg, South Carolina
      Charleston, South Carolina
      Milwaukee, Wisconsin
      St. Louis, Missouri
      Tampa, Florida
      Sarasota, Florida
      Omaha, Nebraska
      New Orleans, Louisiana
      Oklahoma City, Oklahoma
      Dallas, Texas
      Fort Worth, Texas
      San Antonio, Texas
      Colorado Springs, Colorado
      Tuscon, Arizona
      St. George, Utah
      Fresno, California
      Palo Alto, California

      Seems like a lot of testing sites for 124 subjects.
       
      • Like Like x 2
      • Agree Agree x 2
      • Funny Funny x 1
    2. Chad Lawton

      Chad Lawton Member

      Tinnitus Since:
      2/19/18
      Cause of Tinnitus:
      Possible Ototoxicity + Noise Exposure
      I speculate it is for 2 reasons.

      One is that it is another way to mitigate bias by diversifying across more testing sites and the second reason being they are probably looking to make up for lost ground due to the last failed phase 2 trial and speed things up by only needing each site to enroll no more than 5 patients each.
       
      • Genius Genius x 1
      • Winner Winner x 1
    3. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      Where did you get that list from? I only see the 3 sites on the ClinicalTrials website.
       
    4. AfroSnowman
      Balanced

      AfroSnowman Member Podcast Patron Benefactor

      Tinnitus Since:
      April 16 2019
      Cause of Tinnitus:
      Nonnatural energy source
      Well this looks like there might be some new information in this one.

      “At the event, Frequency’s clinical leaders will provide a detailed review of data from nearly 170 subjects dosed with FX-322. A rigorous statistical analysis of these clinical data uncovered the patient populations most likely to benefit from FX-322”

      Also are they referencing a new drug or just a different protocol?
      • A new candidate to treat sensorineural hearing loss that delivers a regenerative therapeutic that may provide greater coverage and increased potency at the site of action within the inner ear, that may enable the treatment of different SNHL patient populations at varying dose levels
      https://frequencytx.gcs-web.com/new...utics-virtual-rd-event-detail-fx-322-clinical
       
    5. Gorbeh3

      Gorbeh3 Member

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Hearing Loss
      More information --> Additional information link

      https://www.clarahealth.com/studies/hearing-study

      Another thing

      Exclusion Criteria: Evidence of or previous diagnosis of auditory neuropathy, traumatic brain injury, "central" hearing loss, or "genetic hearing loss".

      Is that not incredibly vague? How can you even confirm if you have genetic hearing loss? Pretty much all of us have probably been exposed to loud music/noise, probably certain drugs, or just the effect of aging on hearing.
       
      • Like Like x 1
    6. Chad Lawton

      Chad Lawton Member

      Tinnitus Since:
      2/19/18
      Cause of Tinnitus:
      Possible Ototoxicity + Noise Exposure
      Frequency Therapeutics Virtual R&D Event to Detail FX-322 Clinical Advances, a New Program for Hearing Restoration and In Vivo Data from its MS Remyelination Program

      https://investors.frequencytx.com/n...utics-virtual-rd-event-detail-fx-322-clinical

      "Company to Introduce a Second Hearing Restoration Program with a Differentiated Biological Profile and Greater Coverage into the Cochlea, Providing Potential to Expand Addressable SNHL Patient Populations"

      Sounds like they have their next generation version of FX-322.
       
      • Optimistic Optimistic x 1
    7. UHPTS
      Wishful

      UHPTS Member

      Tinnitus Since:
      October 2019
      Cause of Tinnitus:
      Ear infection
      I suppose you can draw the same conclusion as if your grandma was not able to have children, then your mother was not able to have children and now it's you in the same situation, well this is clearly genetic. The same goes for hearing. If your grandma was deaf, ...
       
      • Like Like x 1
    8. dmorg

      dmorg Member Benefactor

      Location:
      Philadelphia, United States
      Tinnitus Since:
      2011
      Cause of Tinnitus:
      don't know, hearing loss related?
      Let’s hope so.
       
    9. 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
      New candidate = New / Reformulated drug.
       
    10. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      The Phase I results have been consistently overblown in this thread. Calling a handful of people "super responders" who appeared to do well in an initial safety test is meaningless in light of a rigorous Phase II evaluation of almost 100 people in which the drug showed no signal - no difference from placebo.

      On the face of it (your term), the reason a drug doesn't show any signal is because it doesn't work.

      Everything else, all the poetic explanations (over-watering the grass, participant bias, etc) is speculation, theory, marketing, spin. And maybe one of these speculative explanations might turn out to be true, wouldn't that be great!

      But let's be honest. The drug didn't work.

      And where we are now is simply hoping that this very talented team of drug developers can develop something real, something that does work, from their early promising leads.
       
      • Like Like x 2
      • Agree Agree x 1
    11. Tau
      In pain

      Tau Member

      Location:
      Europe
      Tinnitus Since:
      2019
      Cause of Tinnitus:
      2019-Concert, 2021-headphones/acoustic trauma at 110dB,16kHz
      Interesting that auditory neuropathy is a criterion for exclusion; I thought the drug ideally would regrow IHCs which would then reconnect to the SGNs, thus fixing synaptopathy (one of the subtypes of auditory neuropathy).
       
    12. Chad Lawton

      Chad Lawton Member

      Tinnitus Since:
      2/19/18
      Cause of Tinnitus:
      Possible Ototoxicity + Noise Exposure
      You're correct it showed no benefit over placebo but also remember that the placebo group showed a positive response never before documented in history.

      For example, one placebo subject had 28 words correct at baseline and 47 words correct at day 90. When comparing the drug group versus the placebo group, they couldn't tell them apart; which tells us the drug group also saw similar improvements.

      It then boils down to the question of which is more likely:

      The drug group had a positive response but the trial was designed poorly and also allowed the placebo group to respond to an equal degree.

      OR

      FX-322 has no effect and sugar water injections to the middle ear improve hearing to a degree never before documented in history.
       
      • Winner Winner x 2
      • Agree Agree x 1
    13. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      I'm confused. So, they are rolling out a brand new drug, separate from FX-322?
       
    14. 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
      Actually, if you had been reading the PR from Frequency Therapeutics, the reason the Phase 2 failed wasn't because the drug group showed NO signal. It was that the placebo group ALSO improved, which made them indistinguishable from the drug group who also showed improvement. This unexpected improvement from the placebo group was not what had been seen in prior validated trials.

      When you miss this detail: that placebo improved AND drug improved in Phase 2A, it leads to mis-information, and emotional response about the drug and firm's position.
       
      • Optimistic Optimistic x 1
    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
      We'll find out. The way that I read it, they are planning to discuss a new development / improved version of FX-322.
       
      • Like Like x 1
    16. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      If they are rolling out a new version of FX-322, I don't know why anyone would want to sign up for their current trial.
       
    17. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      Because bias, and the word score boost attributed to bias, was equally distributed between participants who received the drug and participants who received the placebo, if the drug worked, the group that received the drug would still score higher than the group that didn't because their scores would combine the bias boost with an actual drug boost.

      In other words, let's say the boost from bias, or poor design, or lying, is X. And let's say the boost from the drug is Y.

      In the trial, X is evenly distributed between drug recipients and placebo recipients.

      If the drug worked, the group that got the drug would score even higher, X + Y, because they would get a boost from the drug on top of the boost from bias. But that didn't happen. Everyone showed the same boost, the boost from poor trial design, bias, lying, however you describe it, with no advantage for participants who received the drug.

      Therefore, it doesn't really boil down to your two options because they don't take into account the fact that no one knew which group they were in. Poor trial design boosted everyone, and what we're left with is a drug that failed to produce a signal on top of that.
       
      • Agree Agree x 1
    18. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      What you describe (what happened) is exactly a drug showing no signal at all.

      If there's no advantage for the group receiving the drug above and beyond the bias boost impacting everyone, the drug has shown no signal.
       
    19. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      So if no one benefitted from the medicine then, explain why those who received it subsequently demonstrated improvement?

      I think that @Chad Lawton summed things up quite well with his comment.
       
      • Agree Agree x 2
    20. UHPTS
      Wishful

      UHPTS Member

      Tinnitus Since:
      October 2019
      Cause of Tinnitus:
      Ear infection
      Congratulations @Jack V, you are the 20th person to start this subject all over again! Yeah.
       
      • Funny Funny x 2
      • Winner Winner x 2
      • Like Like x 1
    21. 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 believe the drug can still provide a benefit to a specific population. The new candidate could be years away, and require a whole new series of trials. Therefore, it would be beneficial to the business and patient population to have a drug that works okay for a small group, than wait many many more years for one that works better for a larger group.
       
      • Agree Agree x 2
    22. 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
      This has been discussed so many times. If that is the case, then how would we explain in the Phase 2A having the placebo group see improvements AND the drug group see improvements. While in the other Phase 1/2 and 1b, the placebo group DID NOT see improvements, but the drug group DID.

      This points to a trial design problem, not a drug problem. Hence the Phase 2B that is active and recruiting right now.
       
      • Like Like x 3
    23. Chad Lawton

      Chad Lawton Member

      Tinnitus Since:
      2/19/18
      Cause of Tinnitus:
      Possible Ototoxicity + Noise Exposure
      Agreed. If the improvements we have been seeing were one giant placebo effect across all the trials, regardless of if the drug works or not, you would expect to see about 33% of patients respond in the presbycusis trial but no one responded in either the drug arm or placebo arm.
      But if the bias is in the form of some subjects lying out of desperation to get into the trial, that is not a bias boost that is impacting everyone.
       
      • Agree Agree x 1
    24. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      Thread's like a car, bro. Got to start it up from time to time or the battery dies. :cool:
       
    25. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      There's a great deal of conjecture in this thread about what that "improvement" actually was, and I'm not sure there's anything productive about diving down that rabbit hole again.

      Drug trials often show early promise only to flame out in later, more rigorous trials. That's where we are with FX-322. It showed early promise and flamed out in its most rigorous, definitive study.

      Hopefully - hopefully - this failure is simply a stepping stone to future success.
       
    26. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      Phase 2A drug and placebo groups saw improvements, and the same improvements, because they were both equally benefiting from the same flawed trial design. If the drug worked, you would expect to see improvements above and beyond the improvement experienced by everyone. It's the fact that everyone experienced the same improvement that is so damning.

      There are other explanations why a handful of participants in early trials seemed to have demonstrated improvements, some we might guess at, some we might not, but that becomes irrelevant in light of a larger, more rigorous study.

      If there was something promising demonstrated in early trials with a handful people, something real, let's hope they discover and develop what that was.
       
    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
      So why are they doing a Phase 2B with the same drug and basically the same inclusion/exclusion criteria? Why would they spend the resources on this trial if the drug doesn’t work?

      You seem confident on the subject, I’d like to know the reason?
       
      • Good Question Good Question x 1
    28. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      It impacts the whole study. After all, the liars weren't just put in the placebo cohort, they're also in the drug cohort. Therefore, if the drug worked, the liars get doubly boosted: whatever boost they get from the drug on top of the boost they get from the lie. But that didn't happen. There's only an even increase across all groups, and no signal from the drug. No pop, even among liars receiving FX-322 (which you would expect if it worked).
       
    29. Jack V

      Jack V Member Benefactor

      Tinnitus Since:
      1/2020
      I have no idea why they are doing a Phase 2B trial because I don't know what they know. Maybe they've figured something out and are on the verge of a breakthrough. Maybe they're posturing for their investors. Hopefully the former, not the latter.
       
    30. 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
      Ok. It’s the same exact drug, delivered the same exact way to basically the same class of patients.

      The differences are 1 dose, a 1:1 drug-placebo group size, and the addition of lead-in tests to reduce baseline inconsistencies.

      The drug is unchanged. All of those differences point to trial design.

      What am I missing?
       
      • Good Question Good Question x 1
Loading...

Share This Page