Frequency Therapeutics — Hearing Loss Regeneration

[ErikaS]

Not sure if anyone could provide input on this for me, but I'm wondering if FX-322 would only be for those who present with hearing loss on what is tested on the general/speech range audiogram (up to 8,000 Hz), or would they consider this for those who show "within normal limits" up to 8,000 Hz, but have a distinct unilateral higher frequency hearing difference/loss (10,000 Hz and up) and who present with sound distortions, tinnitus, hyperacusis etc.

I understand and respect that their sole focus is hearing loss and to improve hearing clarity of speech and not tinnitus and/or hyperacusis, but if by some miracle one gained hearing back that reduced/eliminated tinnitus and/or hyperacusis, that in my opinion is just as relevant, as long as drug administration side affects stay low risk.

 

[Lucifer]

Not sure if anyone could provide input on this for me, but I'm wondering if FX-322 would only be for those who present with hearing loss on what is tested on the general/speech range audiogram (up to 8,000 Hz), or would they consider this for those who show "within normal limits" up to 8,000 Hz, but have a distinct unilateral higher frequency hearing difference/loss (10,000 Hz and up) and who present with sound distortions, tinnitus, hyperacusis etc.

I understand and respect that their sole focus is hearing loss and to improve hearing clarity of speech and not tinnitus and/or hyperacusis, but if by some miracle one gained hearing back that reduced/eliminated tinnitus and/or hyperacusis, that in my opinion is just as relevant, as long as drug administration side affects stay low risk.

If you have tinnitus or hyperacusis, you have hearing damage even if your audiograms look normal since they usually test up to 8 kHz. In the earlier clinical trials a few of the patients had audiogram improvements at 8 kHz which was the max that was tested. If they tested up to 16-20 kHz, we could have seen more patients with audiogram improvements. In the Phase 2b trial they are testing at higher frequencies to see if there are audiogram improvements so we should know the results by the end of Q1.

 

[Fightthearmy]

If you have tinnitus or hyperacusis, you have hearing damage even if your audiograms look normal since they usually test up to 8 kHz. In the earlier clinical trials a few of the patients had audiogram improvements at 8 kHz which was the max that was tested. If they tested up to 16-20 kHz, we could have seen more patients with audiogram improvements. In the Phase 2b trial they are testing at higher frequencies to see if there are audiogram improvements so we should know the results by the end of Q1.

Nonsense. I'll reiterate:

Do you know that an audiogram measures pitches only at discrete frequencies? The tiny strips of frequencies that you've lost, which contribute to your tinnitus, are so scarcely distributed in your hearing range that you'd need a far more accurate test to detect them. This was mentioned on a video here, maybe the latest one in the Michigan Tinnitus Discovery thread. (Yes, I also scored immaculate on an audiogram.)

It's mentioned here:

 

[CRGC]

Not sure if anyone could provide input on this for me, but I'm wondering if FX-322 would only be for those who present with hearing loss on what is tested on the general/speech range audiogram (up to 8,000 Hz), or would they consider this for those who show "within normal limits" up to 8,000 Hz, but have a distinct unilateral higher frequency hearing difference/loss (10,000 Hz and up) and who present with sound distortions, tinnitus, hyperacusis etc.

I understand and respect that their sole focus is hearing loss and to improve hearing clarity of speech and not tinnitus and/or hyperacusis, but if by some miracle one gained hearing back that reduced/eliminated tinnitus and/or hyperacusis, that in my opinion is just as relevant, as long as drug administration side affects stay low risk.

As slide 7 on Frequency Therapeutics' corporate presentation illustrates, FX-322 reaches mostly the outermost portion of the cochlea, which is the zone responsible for hearing very high frequencies (between 8 kHz and 20 kHz). So I don't see a reason for it not be effective for someone who only has damage in that area of the cochlea. It could actually be the opposite: more effective for people who only have damage in the very high frequencies.

Here is a link to their latest presentation:
https://investors.frequencytx.com/static-files/3f7523cd-4ffa-4068-b346-41b9ba8c5083

 

[ErikaS]

As slide 7 on Frequency Therapeutics' corporate presentation illustrates, FX-322 reaches mostly the outermost portion of the cochlea, which is the zone responsible for hearing very high frequencies (between 8 kHz and 20 kHz). So I don't see a reason for it not be effective for someone who only has damage in that area of the cochlea. It could actually be the opposite: more effective for people who only have damage in the very high frequencies.

Here is a link to their latest presentation:
https://investors.frequencytx.com/static-files/3f7523cd-4ffa-4068-b346-41b9ba8c5083

Thanks, @CRGC I appreciate your feedback and helping me out!

If you have tinnitus or hyperacusis, you have hearing damage even if your audiograms look normal since they usually test up to 8 kHz. In the earlier clinical trials a few of the patients had audiogram improvements at 8 kHz which was the max that was tested. If they tested up to 16-20 kHz, we could have seen more patients with audiogram improvements. In the Phase 2b trial they are testing at higher frequencies to see if there are audiogram improvements so we should know the results by the end of Q1.

@Lucifer, thank you for your input and feedback! Let's hope we see some improvements in those areas with Phase 2b results!

 

[in_LA]

If you have tinnitus or hyperacusis, you have hearing damage even if your audiograms look normal since they usually test up to 8 kHz. In the earlier clinical trials a few of the patients had audiogram improvements at 8 kHz which was the max that was tested. If they tested up to 16-20 kHz, we could have seen more patients with audiogram improvements. In the Phase 2b trial they are testing at higher frequencies to see if there are audiogram improvements so we should know the results by the end of Q1.

How long does the hearing regeneration last? I heard somewhere that it only lasts 2 years. Is this true? I thought this would be a permanent gain?

 

[Artemis2K]

How long does the hearing regeneration last? I heard somewhere that it only lasts 2 years. Is this true? I thought this would be a permanent gain?

No, that's probably just the maximum time they tested it. They just moved on to next thing.

 

[SmallRonnie]

How long does the hearing regeneration last? I heard somewhere that it only lasts 2 years. Is this true? I thought this would be a permanent gain?

Even if you had to go get another shot every year or so, that would be well worth it. I'd get a shot once a week if I had to.

 

[CRGC]

Even if you had to go get another shot every year or so, that would be well worth it. I'd get a shot once a week if I had to.

Having had three intratympanic shots over three weeks, I'd argue that once a week would make me think twice about it. Especially given the fact that the more holes pierced in your eardrum, the higher the risk of an adverse event.

 

[Chad Lawton]

Not sure if anyone could provide input on this for me, but I'm wondering if FX-322 would only be for those who present with hearing loss on what is tested on the general/speech range audiogram (up to 8,000 Hz), or would they consider this for those who show "within normal limits" up to 8,000 Hz, but have a distinct unilateral higher frequency hearing difference/loss (10,000 Hz and up) and who present with sound distortions, tinnitus, hyperacusis etc.

I understand and respect that their sole focus is hearing loss and to improve hearing clarity of speech and not tinnitus and/or hyperacusis, but if by some miracle one gained hearing back that reduced/eliminated tinnitus and/or hyperacusis, that in my opinion is just as relevant, as long as drug administration side affects stay low risk.

FREQ is currently targeting the moderate to moderately-severe range of hearing loss patients in the noise induced and sudden etiologies for the Phase 2b trial but that doesn't mean it can't be tried by patients outside of those ranges once it is successfully commercialized. The company had a couple of otolaryngologists on their December 13th presentation and were asked a similar question to yours in the Q&A. Both doctors agreed that because FX-322 has such a good safety profile to date that they could see it being used off label by a wide range of patients, even if they fall outside the bounds of the Phase 2b's current target population. Their philosophy was "well it doesn't hurt to try it".

 

[Chad Lawton]

How long does the hearing regeneration last? I heard somewhere that it only lasts 2 years. Is this true? I thought this would be a permanent gain?

With the nature of how they are regenerating the hair cells, it is supposed to be permanent. You may have read "responses lasted 1-2 years" but that does not mean the responses didn't or couldn't have lasted longer than that, it just means 1-2 years was as far out as they tested so far to date.

 

[ErikaS]

FREQ is currently targeting the moderate to moderately-severe range of hearing loss patients in the noise induced and sudden etiologies for the Phase 2b trial but that doesn't mean it can't be tried by patients outside of those ranges once it is successfully commercialized. The company had a couple of otolaryngologists on their December 13th presentation and were asked a similar question to yours in the Q&A. Both doctors agreed that because FX-322 has such a good safety profile to date that they could see it being used off label by a wide range of patients, even if they fall outside the bounds of the Phase 2b's current target population. Their philosophy was "well it doesn't hurt to try it".

Those were exactly my thoughts. I had sudden hearing loss in my right ear caused by an ear infection at the higher frequencies (12,000 Hz and up) which is what brought on my tinnitus. This loss was only recently discovered unfortunately (4 months too late), but even though I am way outside of recovery window with a steroid shot, my ENT let me try two shots to my right ear to see if any difference in tinnitus. There was none, but it was good to know I could try due to low risk factor. Happy to hear that could be the case with FX-322.

 

[Diesel]

With the nature of how they are regenerating the hair cells, it is supposed to be permanent. You may have read "responses lasted 1-2 years" but that does not mean the responses didn't or couldn't have lasted longer than that, it just means 1-2 years was as far out as they tested so far to date.

It should be noted that the drug cannot provide a permanent gain, either. It has demonstrated that to some extent it is causing the regeneration of original hair cells or hair-like cells. The original cells we are born with aren't permanently durable, and neither will be the regenerated cells. (Otherwise, we wouldn't need this site or the drug.)

 

[in_LA]

It should be noted that the drug cannot provide a permanent gain, either. It has demonstrated that to some extent it is causing the regeneration of original hair cells or hair-like cells. The original cells we are born with aren't permanently durable, and neither will be the regenerated cells. (Otherwise, we wouldn't need this site or the drug.)

Correct, but the hair cells should in theory last a lifetime, as long as we take care of our ears, right? Of course there will always be general noise pollution if you live in the city and that may do some damage but I could only hope the hair cells would last until we start damaging them again?

 

[scotty03874]

Correct, but the hair cells should in theory last a lifetime, as long as we take care of our ears, right? Of course there will always be general noise pollution if you live in the city and that may do some damage but I could only hope the hair cells would last until we start damaging them again?

They should if you protect your ears. Avoid concerts, nightclubs, and don't full blast earbuds etc.

 

[Jonno02]

I wonder if anybody out there has a mutation that allows their hair cells to regenerate naturally. As it's not visible, it's one of those silent mutations we'd probably never be able to identify on purpose.

 

[Artemis2K]

I wonder if anybody out there has a mutation that allows their hair cells to regenerate naturally. As it's not visible, it's one of those silent mutations we'd probably never be able to identify on purpose.

I also wonder if it's possible to do genetic modification to be able to do that.

 

[ErikaS]

So if the Q1 shows significant results and use of FX-322, would the next step be FDA approval? Also, wondering if the approval of an intratympanic shot would take as long as oral medication, especially with its safety profile.

 

[SmallRonnie]

So if the Q1 shows significant results and use of FX-322, would the next step be FDA approval? Also, wondering if the approval of an intratympanic shot would take as long as oral medication, especially with its safety profile.

They would still need to do a Phase 3 trial which would take a few more years to complete if everything goes well. It is not certain that it will make it to market but it's minimum 3 or 4 years away if everything goes well.

 

[Lucifer]

They would still need to do a Phase 3 trial which would take a few more years to complete if everything goes well. It is not certain that it will make it to market but it's minimum 3 or 4 years away if everything goes well.

FX-322 Phase 3 clinical trial would take awhile as they need to test more patients. I hope there's a way to speed up the process of getting it approved out into the market while still continuing with the Phase 3 trial.

 

[Diesel]

Correct, but the hair cells should in theory last a lifetime, as long as we take care of our ears, right? Of course there will always be general noise pollution if you live in the city and that may do some damage but I could only hope the hair cells would last until we start damaging them again?

It depends, but until a few million people have sampled the drug in their ears, one can only speculate. I suspect genetic conditions play a factor too. Me, my sister, brother, and father all started experiencing some level of tinnitus / hearing loss in our 30s. Stands to reason that 25-30 years may have just been as long as ours could last... I wouldn't expect the reproductions to be as good as the original.

 

[SmallRonnie]

FX-322 Phase 3 clinical trial would take awhile as they need to test more patients. I hope there's a way to speed up the process of getting it approved out into the market while still continuing with the Phase 3 trial.

They do have the FDA Fast Track which speeds up the process by about 6 months or so. There's a chance they can get to market quicker if the trial results are very good.

Chad Lawton has explained it a lot in this thread.

 

[Fields]

I haven't been following the FREQ thread very closely since the results came out for their last trial.

Back then, the sentiment regarding FX-322 was rather pessimistic. Going through the last few pages now, I'm seeing a much more positive outlook. What has changed?

Do people expect the Phase 2 re-trial to yield significantly better results?

Pardon my ignorance.

 

[Nick47]

I'm seeing a much more positive outlook. What has changed?

@Fields, I'm with you. 20,000 posts on something which would be groundbreaking if it works well, but I'm not at all convinced based on previous trials. I've seen data just as good for OTO-313 and OTO-413 and both failed once the group size expanded.

They have a good PR machine maybe.

Frequency Therapeutics is talked about a lot in support groups, whilst the Dr. Shore's Auricle device has gone under the radar.

Talk is cheap.

 

[InNeedOfHelp]

I haven't been following the FREQ thread very closely since the results came out for their last trial.

Back then, the sentiment regarding FX-322 was rather pessimistic. Going through the last few pages now, I'm seeing a much more positive outlook. What has changed?

Do people expect the Phase 2 re-trial to yield significantly better results?

Pardon my ignorance.

Absolutely. I don't participate in this thread because of the very inconsistent results in the trials. If there is some actual efficacy, the effect would be very modest. The overall positivity in this thread seems to be mainly driven by hope and not science.

The interview on CBS News, sorry to say, seems scripted to me. Just like the switch went off, suddenly it went on again, is what the patient said. It's certain that if there was some kind of efficacy, it would gradually creep in, not be noticeable over days but over weeks/months as connections form. Not instantly. This "super responder" result he is portraying doesn't match the clinical data at all. Frequency Therapeutics is obviously in need of funds and this is one way to create traction. I'd really take this with a grain of salt.

Besides, any form of punction of the eardrum can cause complications such as tinnitus. Our ears are fragile - I would be very hesitant messing with the eardrum and anything related to invasive ear treatments without conclusive results that it will help.

I'm not dismissing FX-322 in full but with such inconsistency, I find it very unlikely this will provide the relief we need.

 

[Artemis2K]

Just because they failed the high dose trial, it doesn't mean it doesn't work. It just means that doing too much at once negates the potential, probably from aggravating the cochlea or washing everything out.

 

[Jonno02]

The overall positivity in this thread seems to be mainly driven by hope and not science.

With an affliction like this, if we don't have hope, we have nothing.

 

[Chad Lawton]

The overall positivity in this thread seems to be mainly driven by hope and not science.

It's certain that if there was some kind of efficacy, it would gradually creep in, not be noticeable over days but over weeks/months as connections form. Not instantly. This "super responder" result he is portraying doesn't match the clinical data at all.

What science or clinical data do you have to prove that hearing can only come back gradually after regenerative treatment? There are too many unknowns for you to be able to dismiss that patient's experience. We don't know if the cochlear hair cell connects to the nerve before the hair cell is fully formed or if it only connects after it's fully matured and ready to work.

The brains of those who have hearing loss but no tinnitus actually went through a rewiring process to tune out the tinnitus, do you have data showing how quickly the brain rewires back to normal once you restore input from the ear? Some people go to bed without tinnitus but wake up with it the next morning so how can you rule out someone's hearing coming back in a similar fashion after treatment?

 

[InNeedOfHelp]

What science or clinical data do you have to prove that hearing can only come back gradually after regenerative treatment? There are too many unknowns for you to be able to dismiss that patient's experience. We don't know if the cochlear hair cell connects to the nerve before the hair cell is fully formed or if it only connects after it's fully matured and ready to work.

The brains of those who have hearing loss but no tinnitus actually went through a rewiring process to tune out the tinnitus, do you have data showing how quickly the brain rewires back to normal once you restore input from the ear? Some people go to bed without tinnitus but wake up with it the next morning so how can you rule out someone's hearing coming back in a similar fashion after treatment?

Is there any medication available for any disease currently that turns a disease/damage/whatever off instantly? Without any form or gradual reduction of symptoms? Even medicines "close" to regeneration such as stem cells do not work instantly but take time and slowly over the course of weeks and months start taking effect. I don't think we need science to draw that conclusion...

Yes, disease/damage can occur instantly. Like tinnitus, losing hearing, or any form of damage. But curing or recovering from any form of damage abruptly, on the spot, like an on/off switch is new for me. Why would this be any different here?

I think, like with each and every other medicine, each individual cell acts differently, depending on how fast the drug is absorbed, what the current state of the cell is, etc. Having all your cells react abruptly and growing simultaneously just makes no sense.

 

[Chad Lawton]

Is there any medication available for any disease currently that turns a disease/damage/whatever off instantly? Without any form or gradual reduction of symptoms? Even medicines "close" to regeneration such as stem cells do not work instantly but take time and slowly over the course of weeks and months start taking effect. I don't think we need science to draw that conclusion...

Yes, disease/damage can occur instantly. Like tinnitus, losing hearing, or any form of damage. But curing or recovering from any form of damage abruptly, on the spot, like an on/off switch is new for me. Why would this be any different here?

I think, like with each and every other medicine, each individual cell acts differently, depending on how fast the drug is absorbed, what the current state of the cell is, etc. Having all your cells react abruptly and growing simultaneously just makes no sense.

Administration of FX-322 didn't reverse his disease instantly, it occurred approximately 30 days after treatment. 4 weeks is not an unreasonable amount of time for immature hair cells to start to communicating with the brain. Who is to say the hair cells didn't start working sooner than 30 days but it was the brain finally rewiring that made it come back instantly? When patients first receive cochlear implants, the implant mapping has to be constantly adjusted as the patients brain goes through the physiological and cognitive changes to adapt to it so why wouldn't the human brain change when you naturally restore signal instead of doing it mechanically.

There are a number of medications/treatments that can reverse a disease or illness within minutes to hours. Psychedelics can potentially reverse depression after a single treatment by helping rewire the brain, epinephrine works within minutes for anaphylaxis, intravenous administration of Valium can relieve anxiety within minutes, etc.