Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
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They are moving on ahead, this is a punch in the gut but the trial was very flawed. There's still a pretty good chance the drug makes it to market.
I take this for now but is hard if they don't show real improvements. 85% to 100% of success.
Sure. Per Frequency Therapeutics, multi dosing may have upset hair cell development ("you don't walk on a seeded lawn..." was their quote). All patients got 4 shots.
The other thing is the problem of faking low word scores for entry into Phase 2a, which Frequency Therapeutics' audiologist said is confirmed because the medical record averages do not match their baseline group averages. This should be *really* obvious if it occurred when it's unblinded though.
The severe group have bad hearing. They don't need to fake anything: neither the EHF to get a lower PTA or a word score.
Honestly, we don't know that definitively, it just seems the most likely scenario.
Given the quotes earlier in this thread with McLean citing "12 days," and with results from Phase 1 showing improvements after just 14 days, I'm not really surprised that they tried weekly doses to accelerate the process. I am surprised, however, at how utterly ineffective it was, and that there was no fallback plan (e.g. varied injection schedules) in case the outcomes were as catastrophic as they turned out to be.
I get why you say this but some people also have really severe dysacusis, hyperacusis and hearing difficulties and tinnitus is just one of the terrible parts of their miserable equation.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
I agree with this that 34% of patients improving 10% or more is not enough but we don't know how much the 66% of patients improved. Some of the patients in the 66% category may have been close to the 10% target. It would have been nice if they had reported how much those patients improved in the 66% category.
So far there is no indication that it "helps" with tinnitus.
I don't understand your optimism.
- May 16, 2017
- 3,754
- Tinnitus Since
- 04/2011
- Cause of Tinnitus
- Syringing + Somatic tinnitus from dental work
I don't understand why for several reasons that the treatment regimen consisted of using four weekly doses, instead of single-dose administrations which is now the plan.
One reason - flooding causing compression of water, sodium and potassium - some other questionable reasons also in article.
The cochlea is filled with a watery liquid, the endolymph,
Cochlea - Wikipedia
One reason - flooding causing compression of water, sodium and potassium - some other questionable reasons also in article.
The cochlea is filled with a watery liquid, the endolymph,
Cochlea - Wikipedia
He used the word unconscious bias but that's clearly the implication (that the scores were not genuine, he just phrased it nicely as not to insult the participants probably):
"Patients, our subjects, they desperately need hearing solutions," said Kevin Franck, Ph.D., senior vice president of strategic marketing and new product planning. "When we communicated there were entry criteria of a depressed word score, we may have induced an unconscious bias in subjects who wanted to get into the trial."
They really should have done 14 days but maybe their thought was quicker dosing might help it get further in negating the "stepping on seeded lawn" problem that they weren't aware of.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
I'm so confused. How can someone have "stability" and lie about their screening scores to get in? Did they not include WR scores as a component of stability? Did they create a trail of lies (>=6 month session and screening)? This seems unlikely.
This is what the clinical trial inclusion criteria says
Also, if the baseline scores were higher than screening, doesn't that sort of mean that there was less placebo cheating? In other words, they may have exaggerated to get in, but felt safe once in to do the baseline and rest of the tests correctly?
This is what the clinical trial inclusion criteria says
2. Established diagnosis of stable sensorineural hearing loss by standard audiometric measures for ≥ 6 months prior to the Screening visit (no changes in air conduction greater than 10 dB at a single frequency or greater than 5 dB at two contiguous frequencies from the prior audiogram to the Screening audiogram in the study ear).
Also, if the baseline scores were higher than screening, doesn't that sort of mean that there was less placebo cheating? In other words, they may have exaggerated to get in, but felt safe once in to do the baseline and rest of the tests correctly?
Otonomy at least has a better drug delivery idea (slow extended release).
Yeah. I don't think they made anyone aware of the pacing of the multiple injections. It's easy for me to look back in hindsight and say "oh shit, no, not that fast, no god please" but I wonder what my opinion would've been had we known beforehand. It's really odd that all schedules followed such a rapid pace though, for sure.
Hard to say I could follow their logic post-facto with these numbers on the board but yeah, who knows.
As in nothing at all happens in any individual? Then yeah, I would say it doesn't work or the delivery method is just atrocious considering it works in explants.
OK WOW, 2 anecdotes.
I can find you 2 anecdotes of low-level lasers helping tinnitus too.Anecdote:
1. a short amusing or interesting story about a real incident or person;
2. an account regarded as unreliable or hearsay.
Either way, it's not being trialed for tinnitus, so... tinnitus would just be an off label thing and so far it's not looking good for hearing loss with these fakes.
I remember you from the scene, it's heartbreaking and scary how tinnitus can destroy healthy and smart brain. I have had tinnitus for 10 years. Last year it got so bad that it literally hurts. I can't say anything optimistic, FX-322 was my last hope. There's no hope now, we're going to die with tinnitus. It's not going anywhere. It's only going to get worse and worse, that's my experience. People who say it gets better ARE LYING.
Re the additional Phase 1b trials that were announced quite out of the blue if remember correctly - I wonder if these studies were made up quickly due to early indication that Phase 2a was not doing well and Frequency Therapeutics needed something to reinforce original trial results and keep an iron in the fire. I could be misinformed on this so shoot it down if need be.
@FGG, @Zugzug, I didn't know that WR was not an important factor in recruitment in Phase 1/2 and this has given me a bit of hope (how about the Phase 1b trials though?). The next Phase 1b studies will be really interesting, however, still not enough to prove anything even if results appear good unless I'm missing something.
I'm coming to the conclusion that worst case scenario is that the good WR result from the Phase 1/2 & 1b trial were fluke, or bias (which I have slightly more confidence that this is unlikely now), or best case scenario it works but can't be proven with audiogram because likely it is down to something like only IHC regenerate, or both IHC and OHC regenerate but only IHC regenerate functionally.
I need to be re-convinced again that FX-322 even works. Good results from the Phase 1b trials will go a way to doing that but not conclusively.
They should just say fuck it and run another Phase 1b study on the home-bound, bed-bound, pain-ridden, crippled tinnitus and noxacusis sufferers and see if we get our social lives, music, careers, family and friend connections, quality of life back.
@FGG, @Zugzug, I didn't know that WR was not an important factor in recruitment in Phase 1/2 and this has given me a bit of hope (how about the Phase 1b trials though?). The next Phase 1b studies will be really interesting, however, still not enough to prove anything even if results appear good unless I'm missing something.
I'm coming to the conclusion that worst case scenario is that the good WR result from the Phase 1/2 & 1b trial were fluke, or bias (which I have slightly more confidence that this is unlikely now), or best case scenario it works but can't be proven with audiogram because likely it is down to something like only IHC regenerate, or both IHC and OHC regenerate but only IHC regenerate functionally.
I need to be re-convinced again that FX-322 even works. Good results from the Phase 1b trials will go a way to doing that but not conclusively.
They should just say fuck it and run another Phase 1b study on the home-bound, bed-bound, pain-ridden, crippled tinnitus and noxacusis sufferers and see if we get our social lives, music, careers, family and friend connections, quality of life back.
You asked, I answered, you don't need to be a jerk; we're all in the same boat here.OK WOW, 2 anecdotes.
Anecdote:
1. a short amusing or interesting story about a real incident or person;
2. an account regarded as unreliable or hearsay.
Either way, it's not being trialed for tinnitus, so... tinnitus would just be an off label thing and so far it's not looking good for hearing loss with these fakes.
I agree with your second statement, however, I believe in the PCA treatment. Science is trial and error. They aren't done.
It's understandable. Maybe we can find out more in May whether there were any tinnitus improvements or not. I still have faith that this will be able to go to the pivotal phase early next year if the severe hearing loss trial shows substantial improvements. Maybe they can let us know out of the 34% of patients that showed 10% or more of word score improvement if any of them were considered to have severe hearing loss.
If the severe category shows no improvements, that means the drug only targets the high frequencies and they may need to develop a new delivery method or they may need additional doses spread out e.g., monthly.
This is my opinion suffering from tinnitus and 4khz deafness.
This is an opinion from the perspective that FX-322 is a drug for deafness.
It may be rough. When it comes to the situation so far... No matter how many injections with a small effect are given in succession, only a small effect can be obtained.
The solution is to make a drug that has a clear effect on the audiogram with a single injection, and then inject it multiple times at non-consecutive intervals, which makes sense.
A single injection was even a little effective. Therefore, there is no choice but to thoroughly improve the performance with a single injection. Difficult. But the only option is that way. After all, they have to rethink pharmaceuticals from scratch. Delivery, concentration, etc. Perhaps it was a recruitment of human resources for pharmaceuticals for that purpose.
I quoted from @Diesel before, there is no choice but to modify the drug in Phase 1b. Otherwise, it will not be a useful drug. If the 10 dB improvement so far is a fluke and that is not possible, then the drug is certainly dead.
In addition, Isn't it Phase 1 and Phase 2 that are undergoing trial and error regarding the number of doses and the amount of drug (in this case, the amount of molecules per dose)?
This is an opinion from the perspective that FX-322 is a drug for deafness.
It may be rough. When it comes to the situation so far... No matter how many injections with a small effect are given in succession, only a small effect can be obtained.
The solution is to make a drug that has a clear effect on the audiogram with a single injection, and then inject it multiple times at non-consecutive intervals, which makes sense.
A single injection was even a little effective. Therefore, there is no choice but to thoroughly improve the performance with a single injection. Difficult. But the only option is that way. After all, they have to rethink pharmaceuticals from scratch. Delivery, concentration, etc. Perhaps it was a recruitment of human resources for pharmaceuticals for that purpose.
I quoted from @Diesel before, there is no choice but to modify the drug in Phase 1b. Otherwise, it will not be a useful drug. If the 10 dB improvement so far is a fluke and that is not possible, then the drug is certainly dead.
In addition, Isn't it Phase 1 and Phase 2 that are undergoing trial and error regarding the number of doses and the amount of drug (in this case, the amount of molecules per dose)?
Something that needs to be said I think...
No-one in this group (including @nightowl) is responsible for the results of this trial. Frequency Therapeutics are responsible for the design of the trial and bear sole responsibility for its flaws. Whatever may have been said on social media should have been taken account of. They are also responsible for the hype that made people so keen to get on the trial in the first place. Them, not us.
Thanks for listening.
No-one in this group (including @nightowl) is responsible for the results of this trial. Frequency Therapeutics are responsible for the design of the trial and bear sole responsibility for its flaws. Whatever may have been said on social media should have been taken account of. They are also responsible for the hype that made people so keen to get on the trial in the first place. Them, not us.
Thanks for listening.
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