MemberI was wondering where this doubt comes from. I thought they were talking about groups as in just Phase 2a subgroups? FX-322 vs placebo etc. instead of groups as in both study groups? I may well have missed the details as I was struggling.
Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
- Start date
Agreed.
43% responder vs. 13% placebo is impressive. Also there was no maximum duration iirc. This drug may work for chronic cases too.
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
They never measured EHF in the original Phase 1 trial. They have measured EHF in the follow up Phase 1 as well as Phase 2 - neither of those trials have shown EHF improvements.
I suspect the answer to your question is that the procedure of injecting the ear itself may or may not have some positive effect on hearing. I know a similar thing has been theorised for Otonomy's Meniere's drug. There must be something seriously weird going on when receiving an ITT injection. I'm going to go away and research this more now.
And just to come back to the original Phase 1 study, the sample size was really, really small, and it would appear that the bears were right: the trial was biased, because all the patients with severely low baselines were in the treatment group. I didn't want to believe this would have an effect, but it did. See graph below:
This quote refers exclusively to Phase 2a. If Phase 2a was really biased as they say, every. single. result. inferred from it is biased. Good results (if there are any) and bad results. Biased results are unreliable and you simply can't assume anything, either good or bad. People lied to enter the study, so that means they also lied (aka faked) about their pre-existing condition.
I just heard it properly. Phase 2a and 1b shows nothing in EHF. It's all based on speech recognition and WR only,
Just a thought. My standard audiogram is normal but my EHF audiogram is a disaster but when I went for my interview they told me this didn't necessarily exclude me if my EHF fit certain criteria. So now I am seriously wondering if the EHF is just as biased too.
Good thought. There are way more LGR5+ cells around IHC than OHC. It seems even with probability, the drug would hit those first. And IHCs are not measured on audiograms.
That is correct. However, Phase 1b did show statistically significant improvements in speech intelligibility and WR. And regarding EHF, they didn't see improvements "at this stage," meaning improvements may appear after day 90.
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
You're missing the point entirely. Even if it was biased - and it probably was, I don't dispute this - why are we not seeing some improvement in both groups in the audiogram? We are seeing no statistically significant differences in word scores and no absolute improvements in either group ANYWHERE on the audiogram. Frequency Therapeutics' entire thesis for WR score recognition improvement, based on their pharmacokinetic models, was that the drug is concentrated in the EHF range which they did not originally test for.
This screams to me that the whole thing is placebo, regardless of what role the patients may have played in getting themselves into the trial. Your point would have more weight if we saw both groups improving in line with the WR improvements over baseline in both groups - biased or not biased. How we now reconcile this with the literature is a huge mystery. I recall @FGG previously speculating whether the act of an ITT injection does something beneficial to the ear, in which case this would also explain why Otividex failed for the exact same reasons - both groups improving without statistically significant differences.
In any case, if your point here is that Phase 2 had different inclusion/exclusion criteria from the follow up Phase 1 study (and was therefore more biased), that point is mute too. Carl LeBel was asked whether patients from the additional Phase 1 study also knew about the WR score entry criteria and he said yes, implying then that the bias existed in both trials.
"Again, our preliminary analysis we do not appear to see anything in the frequency range". The only thing I concede is that it less clear with respect to the Phase 1b trial only as to whether there were was no absolute improvement over baseline or whether there was no statistically significant improvement between the groups.
I understand everyone's frustration and their need for hope and their optimism towards this drug.
But it has been proven that it doesn't work for anything.
There has been no gain in the audiometries, it has no positive effect on tinnitus and they did not examine the EHF. They mentioned it clearly, albeit politically, that single dosing only works for WR, which is not reliable due to mentioned problems during the recruiting process.
It's difficult to accept, but it is what it is in my opinion.
We can only hope for other solutions to work from other companies.
Hey I'm no scientist, but let's just say that at the end of the day they redo the trial with no bias, I think all these companies are definitely on to something and there will be good results.
I however think, no, I almost feel like I know, that the best results, the ideal pinnacle of hearing restoration, will have to come from a combined effort of more than one company. Stem cell research,progenitor cell research, synapse research, nanotechnology, nerve repair, delivery engineering, they need to combine in a harmonious effort.
The ear is a harmonious organ itself, it seems only fitting that the solution will be many different complex concepts coming together working synergistically.
I however think, no, I almost feel like I know, that the best results, the ideal pinnacle of hearing restoration, will have to come from a combined effort of more than one company. Stem cell research,progenitor cell research, synapse research, nanotechnology, nerve repair, delivery engineering, they need to combine in a harmonious effort.
The ear is a harmonious organ itself, it seems only fitting that the solution will be many different complex concepts coming together working synergistically.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
For SIN
The between group p-value was insignificant, but the treated group was, and the placebo group wasn't. I saw this and focused on the treated group because I thought the placebo effect was negligible.
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For WR
[0036] Figure 2 show's improvement in word recognition (WR) scores from a single dose of FX-322. (Figure 2A) Individual WR performance showed improvements as early as day 5, and recoveries were sustained until the endpoint at day 90 (Dashed line=10% change from baseline).
(Figure 2B) FX-322 patients showed increased WR scores across day 5, 30, 60, and 90 whereas the placebo group did not improve; p=0.01, 2-tailed pairwise comparison of adjusted means between treatment groups.
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Today I learned that whether it's foul play or not, inflated placebo improvements is a thing.
There are two scenarios, both are bad.
- Bad: Drug doesn't help audiograms, even in EHF, but legitimately helps WR and SIN. Improvements are obvious within the treatment group. However, the placebo group (foul play or not) also improved, destroying between group evidence.
- Worse: Speech improvements aren't even obvious within the treatment group. If there was foul play, we have to assume with quadruple blinding that there's an equal probability of bad faith (from baseline) in all 4 groups. Therefore, even with the extra kick of deflated baseline scores and dishonesty, the treated group still doesn't see improvements. There's no way to spin this; one would have to believe that, by chance, all of the bad actors landed in the placebo group.
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
I plan on holding. It was money I could afford to lose. I'm interested to see where the 1-dose path goes, and what they plan to do for a parallel multi dose schedule.
Doesn't go to the EHF region which means this is maybe the only region that could be completely faked.
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
I can't reconcile the following, and this is why I have a sliver of positivity:
1. Observing hair cell regrowth in donated human cochlea in vitro
2. Long term results from Phase 1/2
3. No clear placebo bias in open-label study
4. Two other Phase 1bs with data to be released
5. Measuring Fx-322 in cochlea
1. Observing hair cell regrowth in donated human cochlea in vitro
2. Long term results from Phase 1/2
3. No clear placebo bias in open-label study
4. Two other Phase 1bs with data to be released
5. Measuring Fx-322 in cochlea
Keith Handy
Member
- Jan 5, 2021
- 302
- Tinnitus Since
- 11/2020
- Cause of Tinnitus
- Stress + sleep deprivation + noise
How is it even possible to have better word scores and no improvement in the extended audiogram? That's like having no increase in strength, but being able to lift heavier objects anyway.
Exactly. The compound is not dead. But there is probably way more work ahead that we would have hoped.
Rubenslash
Member
Decibel Therapeutics and Otonomy... These are the companies to focus on now.
If I understand correctly, even in the 8-16 kHz, no hair cell regeneration occurred (or at least no measurable improvement on audiogram).
In that case: this drug just doesn't work.
If I understand correctly, even in the 8-16 kHz, no hair cell regeneration occurred (or at least no measurable improvement on audiogram).
In that case: this drug just doesn't work.
This is obviously very disappointing and this drug is probably dead. Word score improvements in 30% of the patients and lack of dose responsiveness is simply killing. First and foremost we need audiogram improvements in the 250-8000 Hz range. This new paradigm that Frequency Therapeutics was pushing since the Phase 1/2 trial with regard to WR scores is just marketing. I also don't believe IT injections are a viable method for sustained, controlled drug delivery.
It's back to the drawing board guys.
It's back to the drawing board guys.
- Sep 21, 2016
- 1,051
- Tinnitus Since
- 2011 - T, 2016- H, relapsed 2019
- Cause of Tinnitus
- noise-induced
I just can't get my head around how they had such solid pre-clinical evidence and the methodology is clearly far superior to other methods, e.g., transdifferentiation. It's interesting what @FGG mentioned about there being more LGR5+ support cells around IHCs than OHCs but then their pre-clinical work demonstrated efficacy in both.
frpp
Member
- Sep 17, 2020
- 196
- Tinnitus Since
- 2010
- Cause of Tinnitus
- Tmj, Nihl, ototoxic drugs, nerve/ vascular issues
Pero1234
Member
- Mar 15, 2018
- 287
- Tinnitus Since
- 02/2018
- Cause of Tinnitus
- home theatre system + high pressure washer
Holding onto my stock. My average purchase price was $23 USD.
I may even buy some more while they are low. FREQ was never so cheap, not even at IPO.
Although I admit it's really scary buying something that just crashed so hard... :-/
I do regret buying some more while they were at $48 USD. I did so against my own better judgement. The higher one buys, the harder one can get hit. I learned my lesson :-(
If they ever rise to those levels again, I will definitely refrain from doing so.
I may even buy some more while they are low. FREQ was never so cheap, not even at IPO.
Although I admit it's really scary buying something that just crashed so hard... :-/
I do regret buying some more while they were at $48 USD. I did so against my own better judgement. The higher one buys, the harder one can get hit. I learned my lesson :-(
If they ever rise to those levels again, I will definitely refrain from doing so.
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