Frequency Therapeutics — Hearing Loss Regeneration

[GlennS]

A lot of tinnitus sufferers have decent audiograms.

That's not the point. FX-322 wasn't initially developed to treat tinnitus. It's meant to restore hearing. So that's what we're initially judging it on. If all it does is solve tinnitus, great, but there are no concrete metrics for that either.

 

[Zugzug]

That's not the point. FX-322 wasn't initially developed to treat tinnitus. It's meant to restore hearing. So that's what we're initially judging it on. If all it does is solve tinnitus, great, but there are no concrete metrics for that either.

I'm so confused. The fact that many tinnitus sufferers have normal audiograms mostly certainly is the point. So you are willing to admit that someone can have tinnitus with normal audiograms, but one cannot have clarity issues with normal audiograms?

Maybe it's just me, but I would think having a medically and publicly misunderstood form of torture would open one's mind. Like, is it that hard to get ahead of the game? Sort of like "I didn't know tinnitus could be that bad with normal audiograms. Maybe people can also have issues understanding speech with normal audiograms? Or hyperacusis or distortions?"

 

[Keith Handy]

A note on audiograms:

Walk up to a piano. Play the lowest "C" on the piano. Now play the next "C", an octave higher. Continue to play C's octave by octave until you've gone the length of the keyboard.

That is how far apart the standard audiogram tones are spaced. There's a universe of untested frequencies between them, even if you add in a couple of G's (3 kHz and/or 6 kHz) towards the high end.

So, even setting the OHC versus IHC discussion aside, even for what the audiogram is supposed to be measuring, it's measuring very little of it. If you have a sharp loss in a narrow band, chances are good that it will fall between the beeps.

 

[GlennS]

I'm so confused. The fact that many tinnitus sufferers have normal audiograms mostly certainly is the point. So you are willing to admit that someone can have tinnitus with normal audiograms, but one cannot have clarity issues with normal audiograms?

Indeed you are confused.

Have you been following the flow of this thread or not?

You have a treatment for hearing loss which may or may not have the byproduct of treating tinnitus. In other words, if it restores hearing, it might also eliminate tinnitus. But if it doesn't restore hearing, it's unlikely to have any beneficial byproduct.

The through-line of the discussion in this thread is that there would naturally be a correlation between people regaining their hearing and the cessation of their tinnitus.

Therefore, what most here (presumably) are expecting to see is, well, IMPROVED HEARING. And what is the first metric one might look for with hearing?

AUDIOGRAMS

How many of those participating in these studies do you think are tinnitus sufferers with normal audiograms? Probably none. So bringing up that cohort in the context of this thread is pointless.

What you are going to have are those with hearing damage who may also be suffering from tinnitus.

If FREQ wants to show that their drug causes no change in audiograms but helps with tinnitus, I'm all for it But so far there's no hard evidence of such nor does the treatment suggest that outcome based on how it is supposed to work.

Will it work in the next Phase 2 with single injections? Definitely not with audiograms, in my opinion.

And if that's the case, I have my doubts that the drug would have much positive impact on tinnitus, at which point I would consider it at best a transitional babystep forward.

 

[GlennS]

A note on audiograms:

Walk up to a piano. Play the lowest "C" on the piano. Now play the next "C", an octave higher. Continue to play C's octave by octave until you've gone the length of the keyboard.

That is how far apart the standard audiogram tones are spaced. There's a universe of untested frequencies between them, even if you add in a couple of G's (3 kHz and/or 6 kHz) towards the high end.

So, even setting the OHC versus IHC discussion aside, even for what the audiogram is supposed to be measuring, it's measuring very little of it. If you have a sharp loss in a narrow band, chances are good that it will fall between the beeps.

Sounds like you're talking about "hidden hearing loss". That may be true but for those with visible degradation in their audiogram, if FX-322 really does blanket the ear in such a way to regenerate all of the hair cells within that area then the audiogram should detect the change. If beyond a certain point it detects it on the way down it should also detect it on the way back up again. If FX-322's effect is very spotty then yes, it might not show actual improvement in the audiogram, but that would still not be saying much in FX-322's favor.

 

[Joeseph Stope]

I'm not going to bore everyone with numbers, I'll just say this:

The fact that they didn't have a lead-in baseline is unthinkable -- and not just in hindsight. I wasn't sure exactly how they did things at screening, but I thought the issue was that they weren't strict enough comparing WR scores from >6 months ago to those at screen.

They seriously did the following: "Hey everyone, we're focused on clarity. We want to see people like the super responders from Phase 1/2. Show me your audiogram from >6 months ago. Oh, thanks. Now take this WR test for baseline. If your score is too high, you won't get in."

It's soul-crushingly incompetent, to the point where it never crossed my mind that they would do things this way.

Now, how much of the overall problem were outright liars (e.g. heard "cat" clear as day and said "not sure") as opposed to some people who unethically stretched the truth in the form of very, very low effort to the point of extreme dishonesty (e.g. heard "cat," but legitimately wasn't sure if it was "cat" or "cap" so said "not sure").

Either way, I pin this on the company. It's a clinical trial for a revolutionary drug and they failed on an extremely elementary trial design aspect.

Regarding the performance itself in Phase 2a: Very poor. Even taking into consideration that they injected four shots into the cochlea in too quick of succession, the drug did not succeed. The responder data looks pretty random. Even with this pitiful trial design error, surely come of these "low effort" participants landed in the treatment group as well. It failed the trial.

I very much hope that the super responders from Phase 1/2 were legit. If so, I think there's some hope for the drug being "good enough" in the next Phase 2, consisting of only single injections.

Maybe you are being a little bit harsh in your critic on the trial design side of things.

You seem to overlook the kind of obtuse policy they have of trying to select only those sufferers who the designers deemed likely to have a high success rate, so the hopeful sufferers, anxious to be included gave them the answers somewhat skewed in the direction of hopefully getting themselves on board in the trial. Hope springs eternal dontcha know?

Well we live & learn by trial and error.

The word recognition scores and the word-in-noise scores seem to me at least to be a more objective and who knows, maybe more scientific criterion of the effectiveness of the drug when compared to some TFI questionnaire of how bothersome do you feel your tinnitus to be now after the trial as compared to how you felt before the trial.

Just sayin'.

 

[Joeseph Stope]

There are more parallels than that. There was also data being spun in both threads.

Neuromod was not without their own charts and data, and then the Tinnitus Talk staff crunched their own extensive report out of the user experiences. Then we all argued over who should be deemed an "improver" or not. Optimists counted anyone who had anything even remotely positive to say in their reports as an improver, no matter how wishy-washy or transitory.

And here, the closest parallel is the emphasis on (admittedly flawed) word recognition scores over audiograms and all this OHC vs. IHC apologia.

You are right that the two treatments are quite different but the hope/hype cycle on display here is following a similar pattern of some people spinning the data in such a way to see what they want to see and disregard what they don't want to see--and then serving that up as if we should all treat it as objective reality. So I wouldn't necessarily lean too heavily on "but this time it's different."

I appreciate your posts very much, even though I would put myself in the optimists' camp rather than the sceptics' camp. You certainly are a voice that should be heard loud and clear.

These past few months gave me something (tinnitus onset since the week before Easter 1992) that made my young again. Something called optimism and hope. Of course it was a big let-down to wake up and find that the trial was a dud, that the share price was reduced to 1/7th and that a class action suit was initiated against the lads at the helm.

If I ever get into media I know the subject for my first All-American soap opera: All these naive sufferers of (you name it: impotence? blindness? Lyme disease? cancer?) pin their hopes on a magic cure and invest money in a cure that they hope will bring them to a new tomorrow. Just in the last week before the results of the pivotal trial comes out this German geezer appears on the boards telling them all that he's a financial expert and that he's pulled out before the big bust. Outrage and derision all round... and then the results prove him -- financially at least -- straight on target.

But don't lose track of the bigger picture. Way back in the 90s and probably before that scientists knew that birds, fishes and some young mammals do actually regenerate hair cells... humans for some reason don't. Now if we could just learn how to imitate nature... wouldn't that be wonderful. It's what we've been doing all along on the path of progress and civilisation up to this.

 

[Joeseph Stope]

Just to fill the place with some optimism let me compare the situation to what it was like in the early nineties:

Back then:
1]. No internet -- at least not to most people. Only to some Puter-Geeks.
2]. No world wide web.
3]. Just infusion therapy (which had a low success rate and many were allergic to).
4]. Not even sound therapy TRT unless the loud version that blocked out tinnitus completely.

Fast forward to 2021 and look how things have changed:
1]. Researchers can spread their knowledge soooo easily by computer.
2]. Tons of research papers coming out each year.
3]. We are organized internationally, globally -- at least here on this board.
4]. They developed the intratympanic injection... so they can at least access the cochlea.
5]. They are getting better at accessing the brain.

Still no cure but one helluva lot better than in the old days.

 

[Joeseph Stope]

Early days yet, but let's just suppose that a treatment appears on the market.

What would a fair price be?

And let's just suppose that said treatments benefits some patients but not others. It would be mighty disappointing to have shelled out forty grand only to find out that the mixture didn't work on you but your colleague who has health cover benefited immensely.

We are such a heterogeneous group and the brain, cochlea, nervous system is so complicated that it seems likely that some people might be lucky winners and the rest of us get left behind.

Like if Dr. Susan Shore's model works out, only you somatic tinnitus people need apply. The rest of us can stay behind and wallow in the sea of noise and hyperacusis.

 

[Chinmoku]

Therefore, what most here (presumably) are expecting to see is, well, IMPROVED HEARING. And what is the first metric one might look for with hearing?

AUDIOGRAMS

How many of those participating in these studies do you think are tinnitus sufferers with normal audiograms? Probably none. So bringing up that cohort in the context of this thread is pointless.

The point some of us have painfully been trying to make is that the audiogram is not the whole story even in assessing hearing, regardless of tinnitus. While it is still a primary measure, and no one is contesting that, we should not disregard treatments that improve different hearing metrics. Frequency Therapeutics is also looking at word scores and is considering otoacoustic emissions if I understood correctly.

A reference:
Perspectives on the Pure-Tone Audiogram

Results:
The pure-tone audiogram provides information as to hearing sensitivity across a selected frequency range. Normal or near-normal pure-tone thresholds sometimes are observed despite cochlear damage. There are a surprising number of patients with acoustic neuromas who have essentially normal pure-tone thresholds. In cases of central deafness, depressed pure-tone thresholds may not accurately reflect the status of the peripheral auditory system. Listening difficulties are seen in the presence of normal pure-tone thresholds. Suprathreshold procedures and a variety of other tests can provide information regarding other and often more central functions of the auditory system.

Conclusions:
The audiogram is a primary tool for determining type, degree, and configuration of hearing loss; however, it provides the clinician with information regarding only hearing sensitivity, and no information about central auditory processing or the auditory processing of real-world signals (i.e., speech, music). The pure-tone audiogram offers limited insight into functional hearing and should be viewed only as a test of hearing sensitivity. Given the limitations of the pure-tone audiogram, a brief overview is provided of available behavioral tests and electrophysiological procedures that are sensitive to the function and integrity of the central auditory system, which provide better diagnostic and rehabilitative information to the clinician and patient.

 

[GBB]

I think it's also important to remember many people here have issues with hearing that have no clear driver, like distortion and reactivity. Assuming that is down to some damaged tissue in the ear, it's nice to think that these vaguely regenerative things could help. My audiograms are fine - it is in other less clear areas where there is a deficit.

 

[ASilverLight]

My audiograms are perfect. Straight up perfect. I have at most a -5 dB dip. My speech in noise test came back at 100%. Yet I have several loud intrusive reactive tones.

Obviously anything that may improve my tinnitus isn't going to improve my audiogram because it's literally impossible to improve on it.

The only reason we cling to audiograms is because it's the only metric of hearing we have. It fails to paint the whole picture, as evident by me and other users.

This is why I'm interested in improvements beyond clear tone audiogram, as are many others.

 

[Keith Handy]

My audiograms are perfect. Straight up perfect. I have at most a -5 dB dip. My speech in noise test came back at 100%. Yet I have several loud intrusive reactive tones.

Obviously anything that may improve my tinnitus isn't going to improve my audiogram because it's literally impossible to improve on it.

The only reason we cling to audiograms is because it's the only metric of hearing we have. It fails to paint the whole picture, as evident by me and other users.

This is why I'm interested in improvements beyond clear tone audiogram, as are many others.

It's not the only metric, but the rest is on point.

 

[RB2014]

My audiograms are perfect. Straight up perfect. I have at most a -5 dB dip. My speech in noise test came back at 100%. Yet I have several loud intrusive reactive tones.

Obviously anything that may improve my tinnitus isn't going to improve my audiogram because it's literally impossible to improve on it.

The only reason we cling to audiograms is because it's the only metric of hearing we have. It fails to paint the whole picture, as evident by me and other users.

This is why I'm interested in improvements beyond clear tone audiogram, as are many others.

We are all looking for something different and that is why the sentiment is so far off between some people on this thread. Those of us that are disappointed were looking for audiogram improvements. To be fair this is a tinnitus forum and not a hearing improvement forum. It was hoped regaining some upper frequencies would help to cure tinnitus. We will see where this ends up.

 

[ASilverLight]

It's not the only metric, but the rest is on point.

Yeah, I know, should've said one of few or the most common but I was in a bit of a hurry but my point stands that it doesn't tell us everything and many of us have perfect audiograms etc, despite having severe tinnitus.

 

[Diesel]

We are all looking for something different and that is why the sentiment is so far off between some people on this thread. Those of us that are disappointed were looking for audiogram improvements. To be fair this is a tinnitus forum and not a hearing improvement forum. It was hoped regaining some upper frequencies would help to cure tinnitus. We will see where this ends up.

There's a really strong correlation between hearing loss/events leading to hearing loss and someone experiencing tinnitus as a symptom. The reason most people are on this forum are for that reason, losing/damaging their hearing and experiencing tinnitus as a result. Also, most of the research and drugs on trials that are popular here have to do with primarily restoring hearing, not resolving tinnitus. It's seems to me that there's a common consensus that restoring hearing = resolving tinnitus.

So, in many ways, this forum is also a hearing loss forum.

 

[Lucifer]

https://investors.frequencytx.com/static-files/a26c03b8-d699-48a5-9bcd-ad980554065b

What I find weird is that some patients who only had 1 or 2 shots of FX-322 got tinnitus as a side effect whereas those patients who got 4 shots of FX-322 didn't experience tinnitus at all.

I reckon it was the placebo shot that caused the tinnitus and not FX-322.

Was there any mention of tinnitus decreasing in the patients that received FX-322?

 

[Zugzug]

We are all looking for something different and that is why the sentiment is so far off between some people on this thread. Those of us that are disappointed were looking for audiogram improvements. To be fair this is a tinnitus forum and not a hearing improvement forum. It was hoped regaining some upper frequencies would help to cure tinnitus. We will see where this ends up.

Respectfully, that's not what's going on.

Everyone, and I mean everyone, is disappointed in the lack of audiogram improvements -- particularly in the high frequency range. It's inaccurate to say "those of us that are disappointed were looking for audiogram improvements." Everyone is disappointed.

Some people deal with failure by looking for silver linings or trying to rationally make sense of the problem. This is not weakness.

To understand my point, let's frame this in a setting that's actually relevant to progress, since you and I are just sufferers talking about this. What if Frequency Therapeutics (or another company in the future) saw the lack of audiogram gains and said "trash the product. We're disappointed and those that think we should keep working on a better product and delivery are loons in denial. We, people who want to give up, are the true disappointed ones!"

Would tinnitus, hyperacusis, or hearing loss ever get cured with this mindset?

Honestly, it's more than a straw man, it's kind of just intellectually dishonest to paint this picture like some of us "don't care" that there aren't audiogram changes. It's just not true. Literally every major contributor to this thread expected audiogram changes and was disappointed when they weren't there.

 

[Diesel]

https://investors.frequencytx.com/static-files/a26c03b8-d699-48a5-9bcd-ad980554065b

What I find weird is that some patients who only had 1 or 2 shots of FX-322 got tinnitus as a side effect whereas those patients who got 4 shots of FX-322 didn't experience tinnitus at all.

I reckon it was the placebo shot that caused the tinnitus and not FX-322.

Was there any mention of tinnitus decreasing in the patients that received FX-322?

They mention in the doc that patients that had tinnitus already continued to report it.

 

[Piney]

https://investors.frequencytx.com/static-files/a26c03b8-d699-48a5-9bcd-ad980554065b

What I find weird is that some patients who only had 1 or 2 shots of FX-322 got tinnitus as a side effect whereas those patients who got 4 shots of FX-322 didn't experience tinnitus at all.

I reckon it was the placebo shot that caused the tinnitus and not FX-322.

Was there any mention of tinnitus decreasing in the patients that received FX-322?

Wait, what? Some people got tinnitus after having the shot? I didn't see that in the report.

 

[kiki]

Everyone, and I mean everyone, is disappointed in the lack of audiogram improvements -- particularly in the high frequency range. It's inaccurate to say "those of us that are disappointed were looking for audiogram improvements." Everyone is disappointed.

Excuse me.

Does "the lack of audiogram improvements" mean "there is no mention of audiograms"?

Excuse me, but is there a statement somewhere on some page that says "there was no improvement in high frequencies"?

https://investors.frequencytx.com/static-files/a26c03b8-d699-48a5-9bcd-ad980554065b

 

[kiki]

Wait, what? Some people got tinnitus after having the shot? I didn't see that in the report.

Isn't an "adverse event" a side effect caused by an injection?

I reckon it was the placebo shot that caused the tinnitus and not FX-322.

However, there is no tinnitus in the placebo group.

 

[kiki]

What does this part on page 2 mean? Is it just about WR? Does that mean that WR, WIN, and PTA (including EHF) did not show any effect over placebo?

In that case, did neither those who received FX-322 nor those who received placebo improve PTA at all? Or was there an improvement in PTA that was forged by as many as WR?

 

[Diesel]

What does this part on page 2 mean? Is it just about WR? Does that mean that WR, WIN, and PTA (including EHF) did not show any effect over placebo?

In that case, did neither those who received FX-322 nor those who received placebo improve PTA at all? Or was there an improvement in PTA that was forged by as many as WR?

View attachment 45433

They're saying that for all measures, the FX-322 treatments group didn't perform better than the placebo group. You can imagine that for WIN, Audiogram, EHF Audiogram, TFI, and whatever else they tested for, that the issues with the placebo group affected these measures as well.

Isn't an "adverse event" a side effect caused by an injection?

However, there is no tinnitus in the placebo group.

View attachment 45432

"Subjects reporting tinnitus had preexisting tinnitus before the study."

 

[kiki]

You can imagine that for WIN, Audiogram, EHF Audiogram, TFI, and whatever else they tested for, that the issues with the placebo group affected these measures as well.

Then, there may be a possibility of improving PTA.
After all, I would like to see detailed data at the individual level.

"Subjects reporting tinnitus had preexisting tinnitus before the study."

Then, it is possible that some of the subjects who did not report tinnitus had existing tinnitus.

 

[Zugzug]

Excuse me.

Does "the lack of audiogram improvements" mean "there is no mention of audiograms"?

Excuse me, but is there a statement somewhere on some page that says "there was no improvement in high frequencies"?

https://investors.frequencytx.com/static-files/a26c03b8-d699-48a5-9bcd-ad980554065b

A lack of mentioning of it is the same thing, just spun. Why would they have noteworthy audiogram improvements and not mention it? It's like the number one thing they are hoping for...

 

[Ali.sy]

Can you summarize what happened in a few lines, to understand what happened?

 

[Lucifer]

Can you summarize what happened in a few lines, to understand what happened?

Yea, I made a mistake before where I thought that those who got placebo shots got tinnitus but the table said those that got placebo didn't get tinnitus.

The only thing I'm not sure of is that after they got the first shot of FX-322, and then 3 shots of placebo, did the tinnitus still stay after that first shot of FX-322?

 

[ThomasRobert]

Frequency Therapeutics claims that FX-322 improves word recognition in mild to moderate cases (sensorineural hearing loss).

Poll: How truthful do you think that is?

Truthful, enough evidence gathered, I trust their claim → Give this post a Thumbs Up.

Confused, still early to tell → Give this post a Hug.

Not true, they are still working out on the drug itself → Give this post a Heart.

 

[Rajin]

Can they take hair cells from people about to die, freezing the hair cells, and transfer to other people? Why is nobody looking at this?