Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

I'm really hoping that Frequency Therapeutics decide on a lower price than that.

$2000 initially plus $500 for each additional shot is still a substantial amount. Unless they have payment plans for such things, for those of us that don't have medical health insurance.

Are you in the US? Care Credit could be used even if their interest rates after the introductory period are pretty predatory. Would be worth it though.

 

[Michael01]

Are you in the US? Care Credit could be used even if their interest rates after the introductory period are pretty predatory. Would be worth it though.

Unfortunately, no. I'm in Australia where we don't have such things.

 

[FGG]

Unfortunately, no. I'm in Australia where we don't have such things.

After a bit of googling, it looks like you have something similar called MediPlan.

 

[tommyd87]

Unfortunately, no. I'm in Australia where we don't have such things.

I don't think that it will be but who knows, the government may simply subside some of it through the PBS and at least for some groups.

I am sure something shall be possibly arranged with the price because if FX-322 or another is ultra successful I can see the government offering it to specific cross sections for nothing.

 

[Jack V]

How long would a person have to avoid swallowing?

2 or 3 weeks.

Just kidding.

My experience with intratympanic injections is that after the injection they roll you onto your side, and you lie there for half an hour with instructions not to swallow. So if it's anything like that, 30 minutes. Of course, they may have an entirely different protocol.

 

[all to gain]

2 or 3 weeks.

Just kidding.

My experience with intratympanic injections is that after the injection they roll you onto your side, and you lie there for half an hour with instructions not to swallow. So if it's anything like that, 30 minutes. Of course, they may have an entirely different protocol.

How the hell does one not swallow for 30 minutes?

That said a former girlfriend didn't swallow for 4 years.

Not kidding

 

[Lucifer]

2 or 3 weeks.

Just kidding.

My experience with intratympanic injections is that after the injection they roll you onto your side, and you lie there for half an hour with instructions not to swallow. So if it's anything like that, 30 minutes. Of course, they may have an entirely different protocol.

Are you allowed to talk during those 30 minutes, or is it essentially swallowing by talking?

 

[Diesel]

2 or 3 weeks.

Just kidding.

My experience with intratympanic injections is that after the injection they roll you onto your side, and you lie there for half an hour with instructions not to swallow. So if it's anything like that, 30 minutes. Of course, they may have an entirely different protocol.

If I recall correctly, they're using a formulation that becomes a gel when it enters the middle ear to keep it in place while the drug enters the cochlea. This should keep it from flowing out of the middle ear and down the throat.

Carl LeBel mentioned, I believe on the Tinnitus Talk Podcast or on HLAA, that patients in the Phase 1/2 experienced symptoms of "ear fullness" for the first 24 hours, that was "probably from the gel sitting in the middle ear."

 

[Lucifer]

If I recall correctly, they're using a formulation that becomes a gel when it enters the middle ear to keep it in place while the drug enters the cochlea. This should keep it from flowing out of the middle ear and down the throat.

Carl LeBel mentioned, I believe on the Tinnitus Talk Podcast or on HLAA, that patients in the Phase 1/2 experienced symptoms of "ear fullness" for the first 24 hours, that was "probably from the gel sitting in the middle ear."

Ok that's good to hear. If we experience fullness from the injection that means the drug is sitting in the middle ear and hopefully it should allow hair cells to regrow.

 

[Chriscom]

Are you allowed to talk during those 30 minutes, or is it essentially swallowing by talking?

When I had my steroid injection to see if it would recover any of my hearing (nope), talking didn't come up--and while I might have said a word or two when they left the room, I think any extensive talking would have drawn attention to my throat and thus swallowing--I'm finding it hard not to swallow while thinking and writing about this!

Btw I could be wrong, but I think they asked me not to swallow for only 20 minutes. Long enough for my taste, it's like trying not to think about an elephant.

 

[tommyd87]

If I recall correctly, they're using a formulation that becomes a gel when it enters the middle ear to keep it in place while the drug enters the cochlea. This should keep it from flowing out of the middle ear and down the throat.

Carl LeBel mentioned, I believe on the Tinnitus Talk Podcast or on HLAA, that patients in the Phase 1/2 experienced symptoms of "ear fullness" for the first 24 hours, that was "probably from the gel sitting in the middle ear."

I thought that there was someone who said that FX-322 is just injected and afterwards you can leave pretty much straight away.

 

[Diesel]

I thought that there was someone who said that FX-322 is just injected and afterwards you can leave pretty much straight away.

I imagine the gel hangs around for a little while? Plus you just had some goop injected into the middle ear... probably going to be a little uncomfortable.

 

[kiki]

Well, for one, apparently anything less than 10 dB is considered insignificant and can be blamed on other factors. Even if 6,000 Hz went up by 5 dB legitimately by FX-322, it's not enough to classify as anything they can actually report on.

As others have stated, this is likely due to the single safety dose simply being used up in the first 9,000 or so Hz and running out prior to being able to raise 6,000 Hz by at least 10 dB. Multiple injections is theorized to overcome this problem.

Thank you for your reply.

"There are molecules that could not be used up between ultra-high frequencies and 9000Hz. Those residual molecules descend to lower levels of 800 0Hz, 6000Hz (and 4000Hz).
The remaining molecules are those that were not used to regenerate the deficient hair cells.
Therefore, with multiple injections, the number of molecules used at higher frequencies will decrease, and the number of remaining molecules will increase. It will reach lower frequencies."​

But,
I am concerned that the unused molecules will not move to lower frequencies.

My thinking is as follows. Immediately after injection, the molecule is located in the center of the lymph and flows, reaching from ultra-high frequencies to 8000 Hz, 6000 Hz (and 4000 Hz), which implants into the supporting cells. Implanted molecules do not emerge in the center of the lymph. Therefore, I think it is difficult for unused molecules to get into the flow of lymph.

Isn't it difficult to get into the lymphatic flow?
Due to precipitation on supporting cells.

I have no academic knowledge, but I am worried.

In Phase 1/2, a group of patients with more severe hearing loss showed improved word recognition scores and a 10 dB improvement at 8000 Hz.
In the group with milder hearing loss, there was no improvement in word recognition scores and no improvement of 10 dB at 8000 Hz.

Are the number of molecules used above 9000 Hz the same in both groups?
I think if the molecule moves to the low frequencies area, the group with milder hearing loss uses fewer molecules above 9000 Hz and more molecules reach up to 8000 Hz.

But, in the group with milder hearing loss, no improvement of 10 dB at 8000 Hz was reported.

Is the reason for this phenomenon because dB is a logarithmic function, so better hearing requires the regeneration of more hair cells for the same 10 dB improvement?

Even if there is no movement of unused molecules to the low frequency area, if the first injection has a slight dB improvement effect, is it possible that the repetition and accumulation will result in 10 dB improvement?

 

[GBB]

I insist on pit stop style ear replacement.

 

[FGG]

I thought that there was someone who said that FX-322 is just injected and afterwards you can leave pretty much straight away.

You have to stay lying down for 10-15 min.

 

[ajc]

Thank you for your reply.

"There are molecules that could not be used up between ultra-high frequencies and 9000Hz. Those residual molecules descend to lower levels of 800 0Hz, 6000Hz (and 4000Hz).
The remaining molecules are those that were not used to regenerate the deficient hair cells.
Therefore, with multiple injections, the number of molecules used at higher frequencies will decrease, and the number of remaining molecules will increase. It will reach lower frequencies."​

But,
I am concerned that the unused molecules will not move to lower frequencies.

My thinking is as follows. Immediately after injection, the molecule is located in the center of the lymph and flows, reaching from ultra-high frequencies to 8000 Hz, 6000 Hz (and 4000 Hz), which implants into the supporting cells. Implanted molecules do not emerge in the center of the lymph. Therefore, I think it is difficult for unused molecules to get into the flow of lymph.

Isn't it difficult to get into the lymphatic flow?
Due to precipitation on supporting cells.

I have no academic knowledge, but I am worried.

In Phase 1/2, a group of patients with more severe hearing loss showed improved word recognition scores and a 10 dB improvement at 8000 Hz.
In the group with milder hearing loss, there was no improvement in word recognition scores and no improvement of 10 dB at 8000 Hz.

Are the number of molecules used above 9000 Hz the same in both groups?
I think if the molecule moves to the low frequencies area, the group with milder hearing loss uses fewer molecules above 9000 Hz and more molecules reach up to 8000 Hz.

But, in the group with milder hearing loss, no improvement of 10 dB at 8000 Hz was reported.

Is the reason for this phenomenon because dB is a logarithmic function, so better hearing requires the regeneration of more hair cells for the same 10 dB improvement?

Even if there is no movement of unused molecules to the low frequency area, if the first injection has a slight dB improvement effect, is it possible that the repetition and accumulation will result in 10 dB improvement?

You are wasting way too much of your time thinking about this, when more will be known in Q2 of 2021. Before that, speculating is futile.

 

[FGG]

Thank you for your reply.

"There are molecules that could not be used up between ultra-high frequencies and 9000Hz. Those residual molecules descend to lower levels of 800 0Hz, 6000Hz (and 4000Hz).
The remaining molecules are those that were not used to regenerate the deficient hair cells.
Therefore, with multiple injections, the number of molecules used at higher frequencies will decrease, and the number of remaining molecules will increase. It will reach lower frequencies."​

But,
I am concerned that the unused molecules will not move to lower frequencies.

My thinking is as follows. Immediately after injection, the molecule is located in the center of the lymph and flows, reaching from ultra-high frequencies to 8000 Hz, 6000 Hz (and 4000 Hz), which implants into the supporting cells. Implanted molecules do not emerge in the center of the lymph. Therefore, I think it is difficult for unused molecules to get into the flow of lymph.

Isn't it difficult to get into the lymphatic flow?
Due to precipitation on supporting cells.

I have no academic knowledge, but I am worried.

In Phase 1/2, a group of patients with more severe hearing loss showed improved word recognition scores and a 10 dB improvement at 8000 Hz.
In the group with milder hearing loss, there was no improvement in word recognition scores and no improvement of 10 dB at 8000 Hz.

Are the number of molecules used above 9000 Hz the same in both groups?
I think if the molecule moves to the low frequencies area, the group with milder hearing loss uses fewer molecules above 9000 Hz and more molecules reach up to 8000 Hz.

But, in the group with milder hearing loss, no improvement of 10 dB at 8000 Hz was reported.

Is the reason for this phenomenon because dB is a logarithmic function, so better hearing requires the regeneration of more hair cells for the same 10 dB improvement?

Even if there is no movement of unused molecules to the low frequency area, if the first injection has a slight dB improvement effect, is it possible that the repetition and accumulation will result in 10 dB improvement?

Some people with normal standard audiograms have horrible extended audiograms. I am one of them. My first audiogram (250 Hz to 8000 Hz) was normal. I have severe to profound loss above 8000 Hz (I have low frequency issues too below 250 Hz).

The people who are more likely to apply for a study with "mild" hearing loss probably did not have normal extended audiograms at all (otherwise why would you bother with a hearing loss study that involves TM puncture?) and without that info we can't know.

You can't extrapolate what you are trying to until phase 2a data comes out unfortunately. So until then, we have to wait.

 

[tommyd87]

Some people with normal standard audiograms have horrible extended audiograms. I am one of them. My first audiogram (250 Hz to 8000 Hz) was normal. I have severe to profound loss above 8000 Hz (I have low frequency issues too below 250 Hz).

The people who are more likely to apply for a study with "mild" hearing loss probably did not have normal extended audiograms at all (otherwise why would you bother with a hearing loss study that involves TM puncture?) and without that info we can't know.

You can't extrapolate what you are trying to until phase 2a data comes out unfortunately. So until then, we have to wait.

I'm in the same boat with extended audiogram and am actually also of the opinion that there could be some people potentially participating in the clinical trial who are in a somewhat same situation when it comes to the very high frequencies. Thus until we see such results come out of the current trial, we won't know what is going to happen with FX-322.

I also wonder where @kiki got the information about how FX-322 is believed to work from? This doesn't make sense that the molecule make-up is different and works at only certain frequencies. I would have thought that the make-up is the same and functions in the same way across the frequencies.

FGG, would you be able to explain what Kiki has said? Thanks!

 

[tommyd87]

I imagine the gel hangs around for a little while? Plus you just had some goop injected into the middle ear... probably going to be a little uncomfortable.

It would be uncomfortable, also if you got the placebo, since that is also a gel.

I don't necessarily think that this is a type of trial that I would like to participate in

 

[weab00]

Some people with normal standard audiograms have horrible extended audiograms. I am one of them. My first audiogram (250 Hz to 8000 Hz) was normal. I have severe to profound loss above 8000 Hz (I have low frequency issues too below 250 Hz).

Yes, that's true. I got an audiogram done from 250 Hz - 8000 Hz and was told my hearing was above average despite having tinnitus/hyperacusis. Therefore my cochlea isn't damaged because of the infallible audiogram that audiologists base everything around. Audiologist told me higher frequencies from 8 kHz - 20 kHz were irrelevant to tinnitus. Baffles me that audiologists don't know about the mechanism behind tinnitus.

How can we expect these people to administer FX-322 to us when they are so out of the loop lol.

 

[tommyd87]

Yes, that's true. I got an audiogram done from 250 Hz - 8000 Hz and was told my hearing was above average despite having tinnitus/hyperacusis. Therefore my cochlea isn't damaged because of the infallible audiogram that audiologists base everything around. Audiologist told me higher frequencies from 8 kHz - 20 kHz were irrelevant to tinnitus. Baffles me that audiologists don't know about the mechanism behind tinnitus.

How can we expect these people to administer FX-322 to us when they are so out of the loop lol.

I too have been told that above 8000 Hz is irrelevant for tinnitus. I think that audiologists working with FX-322 at the start will be the ones who have been specially trained and/or are knowledgeable in what is actually happening.

As a result I reckon that the treatment will continue to be done by people who know what is going on with the medical side or are connected to this through their work within/with an ENT practice.

Many audiologists are not trained in the medical side of this stuff at all or anywhere near what they actually make out to be.

I am also of the belief that in some countries FX-322 could only be available in specially trained ENT clinics or in hospitals.

 

[kiki]

Some people with normal standard audiograms have horrible extended audiograms. I am one of them. My first audiogram (250 Hz to 8000 Hz) was normal. I have severe to profound loss above 8000 Hz (I have low frequency issues too below 250 Hz).

The people who are more likely to apply for a study with "mild" hearing loss probably did not have normal extended audiograms at all (otherwise why would you bother with a hearing loss study that involves TM puncture?) and without that info we can't know.

You can't extrapolate what you are trying to until phase 2a data comes out unfortunately. So until then, we have to wait.

Thank you very much for your reply.

Even with so-called "mild hearing loss", there are patients with severe hair cell loss between the ultra-high range and 8000 Hz. And they are also clinical trial patients with "mild hearing loss". I understood that well.

@FGG, @ajc,
I realized that it was impossible to speculate on how the FX-322 molecule behaves in the cochlea until the Phase 2a results are known. Thank you very much.

@tommyd87,
I'm sorry that my expression is poor and difficult to understand.
I understand that FX-322, like you, works the same at any frequency.
I was worried about how the two molecules move in the cochlea.

 

[Street Novelist]

The waiting until May is going to be excruciating. People will just keep speculating in the meantime.

 

[tarmaced]

How can we expect these people to administer FX-322 to us when they are so out of the loop lol.

Same way doctors actually know very little about HOW what they do works. I mean, you can learn this at med school, but no practicing local GP is going to remember the mechanism by which the all of the drugs they prescribe act, or we wouldn't have enough doctors - the cognitive burden would be way too much. They just know enough process to prescribe and go off-piste with the help of documentation provided by whatever professional body they are hosted by.

The health professionals know enough to fulfil their role as it stands. And their role as described is almost always different from the patient's idea of the role of an ideal healthcare professional, because the patient cares little about the other jobs / admin / time / cost constraints once they are seen (at least where we are unlucky enough to have socialised medicine).

'Needle goes here *poke* - I have done this loads of times, so there is little risk. I have no idea what this stuff does, but the packets says it goes in your ear and will work wonders. Also my fees are very cheap because I am not a unique specialist' sounds good to me.

 

[weab00]

Same way doctors actually know very little about HOW what they do works. I mean, you can learn this at med school, but no practicing local GP is going to remember the mechanism by which the all of the drugs they prescribe act, or we wouldn't have enough doctors - the cognitive burden would be way too much. They just know enough process to prescribe and go off-piste with the help of documentation provided by whatever professional body they are hosted by.

The health professionals know enough to fulfil their role as it stands. And their role as described is almost always different from the patient's idea of the role of an ideal healthcare professional, because the patient cares little about the other jobs / admin / time / cost constraints once they are seen (at least where we are unlucky enough to have socialised medicine).

'Needle goes here *poke* - I have done this loads of times, so there is little risk. I have no idea what this stuff does, but the packets says it goes in your ear and will work wonders. Also my fees are very cheap because I am not a unique specialist' sounds good to me.

I know, it's just funny that the same people telling us hair cells aren't important for tinnitus now will be administering this in a few years.

 

[kamil1364]

Do we know if FX-322 or maybe some synapse-repairing drugs could resolve problem of dysacusis/reactive tinnitus/sound distortion?

I hear a sound very similar to morse code over blowdryers, car engines, white noise (so apparently strongest weapon against tinnitus...), or sometimes even over particular movie scenes/soundtracks (which thankfully is quite rare).

,,Normal" tinnitus is certainly bearable, but I believe I'll have really hard time with dysacusis (or whatever you call it, really).

 

[Diesel]

I know, it's just funny that the same people telling us hair cells aren't important for tinnitus now will be administering this in a few years.

This is why we're observing Frequency Therapeutics make a continuous effort to validate and inform doctors and patients of the benefits of hair cell regrowth so early in the drug development process. They seem highly aware that doctors are not up to date on research and/or treatments in developments, and the enormous patient population need to be informed on progress being made.

 

[Diesel]

Do we know if FX-322 or maybe some synapse-repairing drugs could resolve problem of dysacusis/reactive tinnitus/sound distortion?

I hear a sound very similar to morse code over blowdryers, car engines, white noise (so apparently strongest weapon against tinnitus...), or sometimes even over particular movie scenes/soundtracks (which thankfully is quite rare).

,,Normal" tinnitus is certainly bearable, but I believe I'll have really hard time with dysacusis (or whatever you call it, really).

I experience this myself on occasion.

I think FX-322 will help with this condition. It seems like the underlying issue is likely damaged hair cells sending improper signals to the brain, or the brain trying to compensate for sounds erroneously due to missing hair cells.

If FX-322 works as intended, I think it's possible the following will help reduce the symptom: The damaged/missing cells are replaced with functioning ones, and the brain gets correct signals. The malfunctioning cells stay, but a population of new cells are created in the same area; the increased "bandwidth" of signal from properly function cells dramatically reduces the effect of the dysfunctioning cells.

 

[GBB]

Is there any data to suggest your tinnitus frequency is aligned to the actual frequency of hearing loss? Just trying to intuit some simple stuff here; for example my tinnitus is about 14 kHz, so wondering if because FX-322 hits high frequencies first, I would theoretically be a good candidate.

 

[FGG]

Is there any data to suggest your tinnitus frequency is aligned to the actual frequency of hearing loss? Just trying to intuit some simple stuff here; for example my tinnitus is about 14 kHz, so wondering if because FX-322 hits high frequencies first, I would theoretically be a good candidate.

Can you get an extended audiogram? If you had OHC loss at 14 kHz specifically you could see it on an extended audiogram. Synapse loss alone wouldn't show up though.