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Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
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"A" being a non responder (like B) obviously makes them different than the ones who doubled their word score. So the question is what is it about "A" that makes them not respond like the others even though they had a low word score.
And what is it about the responders that makes them respond?
The answer is likely distribution of lesions or an unaccounted for central effect.
The only other explanation would be that "super responders" were fraud.
Or did you mean "bad news" in terms of guaranteeing results from the severe arm?
- Feb 14, 2020
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What I meant is that we can call it whatever reason -- it could be distribution of lesions -- but it casts doubt that everyone in the severe arm will present with beautiful data. Another thing is seeing Patient B, with a heavy ceiling, improve by ~10% absolute WR, kind of makes the 34% of responders in the open-label study look less impressive.
My guess is there's probably a certain type of person that has the right lesions in the right spot to respond nicely. However, shouldn't the drug have to demonstrate more, even for incremental change? To clear Phase 2, where there has to be clear difference between groups, it seems like what matters more is pervasiveness than just the existence of super responders.
I would find it really pleasantly surprising if the severe trial produced a bunch of nice data. I do hate that there's only 6 placebo patients though, as it doesn't really matter what the placebo data looks like, it's so few data points.
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Being a bear is a breeze. The burden is on the bulls to supply the proof. I just have to eat a lot, take care of my cubs, and wait for some results to rock my world, while always appealing to the tautology that something is unproven by default.
I don't doubt that they will have to repeat Phase 2 to showcase their responders better (been my position all along) but I still think individual data will be highly useful from the severe arm especially.
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I mean like, maybe this formulation and delivery just don't lead to pervasive gains and the next Phase 2 could fail as well. That's my fear.
The silver lining is that a proof of concept in vivo for the right lesion distribution is still a big milestone, but if it's too random, the drug may fail Phase 2 again. As @Diesel and @HootOwl have pointed out, there's not really a perfect test to learn where the IHC lesions are. Hence, getting the right recruitment involves some degree of luck.
On the other hand, if the drug had a slow-release formula, I would feel better that the lesions (at least in >=8 kHz range) were hit in a satisfactory way.
With a single dose Phase 2, you are basically repeating Phase 1 but with a larger cohort. So your odds of finding enough patients to show the drug has a good effect on at least a significant number of people are much better.
But the data from the remaining Phase 1s won't be enough. They need to repeat Phase 2, hopefully with better patient selection and trial design.
The FDA itself usually doesn't make the decisions on how to interpret the data. They have an advisory committee in each specialty. So it would depend who is in the AdCom.
This is what I'm worried about. These people have no clue about IHCs OHCs and synapses. How are they supposed to know that each hearing loss drug treats different things?
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They aren't going to pass a drug over a controversial theory. What would have to happen is the Phase 2 repeat combined with some of the Phase 1 results would have to make it clear that word scores are improving. Then, it's hardly a theory, other than the fine details of like which patches of hair cells are being hit.
If the data demonstrates this effect, it's not like impossible for an otologist to picture that inner hair cells are regenerating. I know we bash them because their knowledge of hyperacusis and tinnitus is meh, but they do know a lot about the ear. They aren't going to have a hard time understanding theories from this forum.
It's the company's job to make a case for their drug and use available knowledge as well as their study's results to do that. The IHC component to hearing isn't at all unknown. It's not like @Diesel and I came up with it. It's pretty well established, just not to most patients (that's why Dr. Cliff made a video explaining it).
As far as there being an IHC preference, word scores show that. The results just need to be reproducible over a larger sample. What happens to OHCs with single dosing is less of a concern if they try to go for approval based on "clarity" effects.
If they can show that and move to Phase 3, I really wouldn't worry about the AdCom unless they have an incredibly muddy Phase 3 but that's super jumping the gun at this point.
If they do, unfortunately it's within 10 dB first pass so there is no way to prove it so you likely wouldn't know how much of an effect in the trials because they have indicated they will proceed with single dose for future trials towards approval.
I do wonder if they plan to do a fully experimental arm at one point looking at multi-dosing with bigger intervals but they may or may not and that would be impossible to speculate on.
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At this point, we're mostly spinning our wheels. I'm starting fights with myself over math and humble bragging about my cute cat for karma points. It's going to be a long wait for end of Q2.
I'm really not sure what you mean by this but no they don't selectively show data. They show all the data and present their findings. I don't think they can cherry pick Phase 2a if that's what you mean. They need to re-recruit and restart the trial as a single dose with a different design.
I don't think using Phase 1 data alone (even with the arms still ongoing) is realistic.
Forever hopeful
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For what it's worth, my neurotologist said hearing in damaged ears fluctuates.
Considering that 10 dB is barely audible and 20 dB is a whisper several feet away, you may not perceive the fluctuations.
Might as well be. It's not a medical forum either but a lot of medical doctors apparently reside here.
True, but I've gone from a 25 dB loss to 70 dB and up and down with farther and farther from baseline each time. Same in the lows. Who knows.
I hope that FX-322 will be marketed as a drug aimed at improving WR and that it will have an improvement in audiogram as a side effect (Side utility).
In that case, I think a certain number of anecdotes are sufficient and no proof is required.
His fluctuation was 20 dB if I recall correctly which definitely wouldn't be considered "stable hearing loss". That's the difference between conversation and a hair dryer.
Edit: nevermind, his fluctuations were even more pronounced.
Just to confirm @Jrblovsky, you said before you couldn't tell the difference in your hearing with these different audiogram results?
Edit #2: lol. What is that at the end of the decibel chart. Lmao. Thanks Google images. I'm leaving it.
But it could be possible though. Hearing loss is an unmet condition. If there is any proof of meaningful word scores and audiogram improvements then FX-322 needs to come out ASAP. It could help millions of people worldwide especially the military who got damage from using crap earplugs by 3M.
It doesn't work that way. It's an unmet need but they still have to show data.
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