MemberIn the Phase 1b trials there were some audiogram improvements but they only went up to 8 kHz. Hopefully with the Phase 2b trials they go up to 20 kHz with audiograms and we should see more people with audiogram improvements.
Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
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- Feb 14, 2020
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HF Audiograms go up to 16 kHz. Above that, and the tools become unreliable. Based on their most recent diagram showing FX-322 penetration into the cochlea, it looks like there may be some improvement from 12 kHz - 16 kHz.
The FDA recently agreed with Frequency Therapeutics that Word Score Measures are an acceptable measurement for real-word/clinical hearing improvement, and the ONLY primary outcome for the Phase 2b. Therefore, I highly doubt we'll see much of anything from the firm on audiogram or tinnitus (TFI) throughout the remaining trials for FX-322. They're now all secondary outcomes, and there's no benefit to analyzing them as long as Word Score is the benchmark to get this drug to approval and market.
The best thing to look at is the RADIAL assessment that they developed. It's a QoL measure, and may be the best derivative indicator for overall life improvements.
Audiogram / TFI might be different for FX-345, though.
Chad Lawton
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I don't see FREQ going bankrupt. Too much promise in their technology & patents both in and out of the hearing space. Progenitor cell activation for MS works as evidenced by multiple Phase 2 clinical trials from multiple educational institutions. I'm confident there MS drug will work, I'm only hesitant about what side effects it may cause and if that could prevent it from making it to market.
AfroSnowman
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Frequency Therapeutics Shares Results from FX-322-113 Severe Sensorineural Hearing Loss Study Showing Speech Perception Improvements in Noise
Does this read that 4 out of 31 saw some improvement? Is this good?
Does this read that 4 out of 31 saw some improvement? Is this good?
- Dec 2, 2019
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Considering that everyone on this thread thought that there'd be no positive news coming from the severe trial, it's actually pretty positive and a step in the right direction.
Science is iterative. Has any treatment before yielded these results? FX-322 is a start. FX-345 might do more.
It's far from a joke. We should be saying "GO FREQUENCY!!!" instead of putting them down when they don't deliver 100% perfect hearing regeneration right off the bat.
It's not all or nothing, it's not now or never, this is progress and can become huge.
Street Novelist
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4/25 got drug. 6 got placebo.
3 dB improvement in a SIN test (Sounds In NOISE -- not audiogram) is significant. About the same as what was seen with OTO-413 (roughly 4 dB improvements), except OTO-413 treated patients with better hearing.
I agree with @2noist, this is iterative. A Phase 1B is a look at a piece of the overall "puzzle" to restoring hearing.
What is not yet known is whether or not those 4 responders are enough to change the acceptance criteria of the Phase 2B. If not, it's a sign that FX-322 probably won't be marketed to patients with a PTA worse than 85 dB.
They state the patient/placebo ratio is 4:1, so there were 25 FX-322 patients and 6 placebo patients. 4/25 (16%) of the FX-322 group saw an improvement and 1/6 (16.6%) of the placebo group saw an improvement. They also state that the improvement was seen in a sound in noise test and don't say anything about a words in quiet test (was there no improvement in words in quiet?). I believe they only checked 1 time point too (90 day).
These results seem pretty grim to me. They're also significantly weaker than OTO-413's Phase 1 results (though in fairness that study was smaller), which is geared towards improving hearing in noise.
Chad Lawton
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2 things:
First is the numbers. It's not 4 out of 31, it's 4 out of 25 as 6 of them got placebo.
Secondly, remember that FX-322 is barely touching the base of the cochlea (as shaded in orange). The fact that 4 patients saw an improvement when they have Severe hearing loss and you are "treating" only the top 15% to 20% of their hearing range while leaving the remaining 80% of their hearing untouched, it is actually pretty promising.
It also bodes well for FX-345 (shaded in purple) as it targets the exact same pathways as 322 but is able to penetrate deeper based on the more potent GSK3 inhibitor. In my opinion, these hit and miss improvements between patients are a result of poor cochlear penetration and not a failed mechanism of action of the drug. It appears that the drug works and just needs to get deeper.
Chad Lawton
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I don't think it's fair to make the comparison to OTO-413 without knowing how deep OTO-413 is penetrating the cochlea. If OTO-413 is reaching the apex while FX-322 is barely reaching the base, that is comparing apples to oranges. The 4 Severe patients saw improvement when FX-322 "treated" only the top 20% of the patient's cochlea while leaving the bottom 80% untouched.
DimLeb
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I wonder why they don't use some high frequency audiogram testing, since they know how far in the cochlea this substance can reach. If it truly regenerated something in there, wouldn't the ability to hear 10 kHz-20kHz sounds come back? I'm no expert of course, but the whole thing about FX-322 looks so off since the beginning.
For some perspective, here is the visualization that they had previously been using for FX-322 (as recently as this past summer):
What's shown here is based off of their 2020 study that "confirmed" delivery to the target area. It's unclear to me why the new visualization looks different (did they examine more cochleas?). Also, check out their original visualization of FX-322 penetration (prior to the 2020 study):
This is from the first half of 2020. They silently updated this visualization after their delivery study. It's hard for me to get excited about their newest visualization when it looks exactly like the original one - one they've continued to silently tweak. Until they come forward with good results that show their drug works, I'm going to be skeptical. They've talked a big game for several years but have yet to really prove themselves.
From the link:
"In the study, subjects did not show substantial changes in speech perception measures in quiet, the safety profile in the study was favorable and there were no treatment-related serious adverse events reported."
This doesn't make sense, how can there be improvements observed in SIN and not in quiet?
"In the study, subjects did not show substantial changes in speech perception measures in quiet, the safety profile in the study was favorable and there were no treatment-related serious adverse events reported."
This doesn't make sense, how can there be improvements observed in SIN and not in quiet?
Chad Lawton
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That is interesting, I hadn't seen much of that image showing FX-322 getting down to 4,000Hz. So it appears that they keep showing FX-322 reaching less & less area with each updated visualization. I'm curious what research & data caused them to do that.
I'm confused because I don't understand the basics clearly.
Were there any articles in animal experiments that they improved hearing in hearing-impaired mice? Was it an article about hair cell regeneration, not hearing restoration?
Has anyone seen an article about hearing restores on all frequencies with a mouse? I feel like I've seen a post with such a quote.
Chad Lawton
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Frequency has said that in their preclinical noise damaged mice models they were able to restore hearing function, I believe they measure it via brainstem response but I could be wrong.
DimLeb
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I don't know a lot to be honest, but they (Frequency Therapeutics) proudly use images of cochleas that have renewed lines of cells. I believe it's from mice since they are not allowed to dissect a human cochlea. Hair cell regeneration shouldn't be too far from hearing restoration, but there are synapses and other nerves in there. But I'm sure there were articles about hearing impaired mice that got their hearing restored.
Voice recognition comes from hearing each frequency that is moving with the voice clearly. Some frequencies are more important, some are not. If there are cells missing, for example at 2050 Hz - 2450 Hz, then you can't register the frequencies of the voice when they go to that region, so you miss part of the word's sound. So you have partly impaired voice recognition.
I don't understand either how they're looking to restore hearing, but by the looks of it, they restore hair cells.
I think that the truth may not be known without animal experiments with mammals that are closer to humans than mice.
But I don't know what kind of animal it is.
Is it only a mouse in the animal experiment of FX-345? I think that's not enough.
For that reason, I'm worried whether the video that FX-345 penetrates deeper is true.
How far is the truth?
That's why I posted about animal experiments.
Exactly. People in this thread are wondering why the results weren't that good and we have to remember this is for participants who have severe hearing loss. We also have to remember that the difference in hearing improvements had to be 3.1 dB or greater. For all we know there may have been more patients who were near a 3.1 dB improvement but unfortunately Frequency Therapeutics aren't going to say the improvements for each patient.
But if 4/25 in the severe hearing loss had a 3.1 dB improvement in hearing or greater in certain frequencies then imagine what the mild-moderately severe hearing loss patients results will look like end of next year.
This may be enough to get rid of tinnitus permanently.
I find it odd that they are not doing any audiogram measurements. I don't think regenerating hair cells for 10 kHz and up would really affect speech perception much. Maybe it would bring some clarity to the sound, but I can't imagine it would be much.
Nonetheless, interesting results and could be promising for FX-345.
Nonetheless, interesting results and could be promising for FX-345.
To be honest, I don't know and understand how significant a 3.1 dB or 6 dB improvement with BKB-SIN is for patients with severe hearing loss.
I also learned for the first time that the index of improvement in BKB-SIN is not "the number of words that can be recognized" but dB.
How is BKB-SIN different from WIN (word in noise) and WR (word recognition)?
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