Frequency Therapeutics — Hearing Loss Regeneration

[chinup]

Doesn't Japan have some expedited drug approval process?

 

[Lucifer]

Doesn't Japan have some expedited drug approval process?

Not sure if they will be doing clinical trials in Japan or anywhere else in the world.

Maybe they could just use USA clinical trials data instead of having to conduct their own clinical trials to get FX-322 approved in those countries. I hope this is the case.

 

[tommyd87]

Not sure if they will be doing clinical trials in Japan or anywhere else in the world.

Maybe they could just use USA clinical trials data instead of having to conduct their own clinical trials to get FX-322 approved in those countries. I hope this is the case.

They definitely will be doing clinical trials outside the US as Europe trials result in Frequency Therapeutics getting their payment from Astellas.

A part of the reason I reckon that the deal was made with Frequency Therapeutics to do trials in Europe was because at the time there was a requirement to conduct trials in Europe in order to gain approval there.

This has since changed with the more recent EU and USA agreement allowing both jurisdictions to recognise one another's trial outcomes, however it is still beneficial for us because it means that the trial candidacy pool is quite probably going to be larger.

 

[Gb3]

Here we go again! If it works, it's definitely going to be on the market!

 

[Gabriel]

I think some people here should be more humble.

I have tinnitus and no acoustic trauma, and no hearing loss in the frequency of my tinnitus.

One of my tinnitus sound is moving from 600 Hz to 800 Hz like a wind whistling.

So what, my hearing loss is moving now too? What's your explanation on that?

And how come my tinnitus wasn't brought on by any acoustic trauma?

It's not as simple as having hearing loss.

Some people experience pain even though they have nothing hurting them, so to paraphrase you "I don't know why it's such a difficult concept to understand"

Oh and what about visual snow? Is it because people have eye trauma?

Tinnitus doesn't always come from outside sources, it can come from within the brain.

Be humble when you speak please.

 

[katri]

I think some people here should be more humble.

I have tinnitus and no acoustic trauma, and no hearing loss in the frequency of my tinnitus.

One of my tinnitus sound is moving from 600 Hz to 800 Hz like a wind whistling.

So what, my hearing loss is moving now too? What's your explanation on that?

And how come my tinnitus wasn't brought on by any acoustic trauma?

It's not as simple as having hearing loss.

Some people experience pain even though they have nothing hurting them, so to paraphrase you "I don't know why it's such a difficult concept to understand"

Oh and what about visual snow? Is it because people have eye trauma?

Tinnitus doesn't always come from outside sources, it can come from within the brain.

Be humble when you speak please.

I understand what you're saying but multiple times here people have said this won't be the end all be all for tinnitus sufferers.

There are over 400 pages of us having discussions, doing research, interviewing researchers, etc. I think it's a little tone deaf to assume that people here aren't humble. I was here when there was little to no hope, then progressively we've received more and more good news. There are people here who have put in countless hours doing their due diligence and never lying to people about what could happen as a result.

You're welcome to look through the hundreds of pages where we've discussed this time and time again. People here just have a little more hope or at least they're trying their best too and for good reason. We should be receiving more information progressively and hopefully it'll be good news.

I hope this answer helps

 

[Lucifer]

I understand what you're saying but multiple times here people have said this won't be the end all be all for tinnitus sufferers.

There are over 400 pages of us having discussions, doing research, interviewing researchers, etc. I think it's a little tone deaf to assume that people here aren't humble. I was here when there was little to no hope, then progressively we've received more and more good news. There are people here who have put in countless hours doing their due diligence and never lying to people about what could happen as a result.

You're welcome to look through the hundreds of pages where we've discussed this time and time again. People here just have a little more hope or at least they're trying their best too and for good reason. We should be receiving more information progressively and hopefully it'll be good news.

I hope this answer helps

The cure will be out soon. I have a good feeling that FX-322 will pass their clinical trials and should be able to help most of us. There has never been a drug before that regrows hair cells and synapses before FX-322.

 

[FGG]

I think some people here should be more humble.

I have tinnitus and no acoustic trauma, and no hearing loss in the frequency of my tinnitus.

One of my tinnitus sound is moving from 600 Hz to 800 Hz like a wind whistling.

So what, my hearing loss is moving now too? What's your explanation on that?

And how come my tinnitus wasn't brought on by any acoustic trauma?

It's not as simple as having hearing loss.

Some people experience pain even though they have nothing hurting them, so to paraphrase you "I don't know why it's such a difficult concept to understand"

Oh and what about visual snow? Is it because people have eye trauma?

Tinnitus doesn't always come from outside sources, it can come from within the brain.

Be humble when you speak please.

No one is saying all tinnitus is from cochlear damage/hearing loss but rather anything that interferes with hearing can cause tinnitus.

That can range from ETD, TMJ, Hydrops, ear drum rupture and even inflammatory conditions.

It's good news that it's not "stuck in the brain" and that neuroplasticity isn't one way like a light switch with the handle broken off.

And yes, things like TMJ aren't technically hearing loss but they do interfere with normal hearing.

Hydrops (for example), can cause fluctuating low frequency tinnitus (not saying you have this, it's literally just an example) but isn't "hearing loss" as much as "hearing interference."

I have personally on here advocated for referring to tinnitus as being caused by "hearing interference" and secondary maladaption by the brain (which is not brain damage and could be reversed when the cause is) rather than saying "hearing loss" for that reason but people who have noise induced, viral or ototoxic causes have hearing loss whether they realize it or not and since this is a thread about regenerative medicine those are the people this drug concerns.

This may not apply to you (and FX-322 isn't designed to treat people without hair cell loss) if you had fluctuating tinnitus caused by ETD, Hydrops, TMJ, middle ear pathology, the list goes on...

Anyway, Dr. Thanos Tzounopoulos was asked about the origin of tinnitus in a webcast and he said the only case he could think of where it truly "originated in the brain" was in schizophrenia. So it probably applies to a really small percentage of us.

 

[d'Wooluf]

Be humble when you speak please.

We're dealing with conditions that are highly complex, variable, and just beginning to be understood (by experts). People try to make things less scary by simplifying the issues in their own minds. Theories become facts, the most obvious possible etiology becomes the only possibly etiology. That may come across as arrogance. It's probably not. Keep that in mind when you browse the forums. Maintain a bit of healthy separation from the daily grind of it. Take away what makes sense to you. Remember that there are people out there with very big brains who progress the science on this stuff every day. There is definitely reason for hope for all of us.

 

[katri]

How many people noticed a change in their tinnitus during the last clinical trial phase? On average, how many people with SNHL have tinnitus?

What if 4/15 noticed substantial improvements in their hearing, while only 10 of them actually had tinnitus. Wouldn't that be important to think about? Maybe you've already talked about this. I'm just a little too far gone to go back 40+ pages.

EDIT: I randomly looked it up. The first thing I saw said only around 30% of people with hearing loss have tinnitus.

 

[antonio77]

On average, how many people with SNHL have tinnitus?

You're in my head, I was thinking just that.

Does everyone with sudden hearing loss have tinnitus? You already know that you can have hearing loss and not have tinnitus, that suggests that it is something more complicated.

 

[tommyd87]

How many people noticed a change in their tinnitus during the last clinical trial phase? On average, how many people with SNHL have tinnitus?

What if 4/15 noticed substantial improvements in their hearing, while only 10 of them actually had tinnitus. Wouldn't that be important to think about? Maybe you've already talked about this. I'm just a little too far gone to go back 40+ pages.

EDIT: I randomly looked it up. The first thing I saw said only around 30% of people with hearing loss have tinnitus.

There was no official reporting on tinnitus because it wasn't even an element of the Phase 1/2 trial. There were anecdotal accounts about tinnitus however from participants which indicated they experienced an improvement in it.

Tinnitus will be discussed in the outcomes maybe as part of the 90 day read-out or as full results are released in July.

 

[katri]

There was no official reporting on tinnitus because it wasn't even an element of the Phase 1/2 trial. There were anecdotal accounts about tinnitus however from participants which indicated they experienced an improvement in it.

Tinnitus will be discussed in the outcomes maybe as part of the 90 day read-out or as full results are released in July.

Thank you! I can understand why people on this thread are excited for the results.

30% is a solid percentage of any group and if they found it important enough to mention, then there's a good reason to push optimism through March/July.

 

[tommyd87]

You're in my head, I was thinking just that.

Does everyone with sudden hearing loss have tinnitus? You already know that you can have hearing loss and not have tinnitus, that suggests that it is something more complicated.

You can also have no hearing loss, but still have tinnitus caused by other factors. From what I can observe this doesn't mean that this then is something more complicated necessarily but rather it is possibly caused by something other than just sudden hearing loss for example.

Examples include the fact that people have tinnitus possibly due to synaptic issues for example.

 

[tommyd87]

Thank you! I can understand why people on this thread are excited for the results.

30% is a solid percentage of any group and if they found it important enough to mention, then there's a good reason to push optimism through March/July.

I think that the other thing that should be mentioned is that it is only for the group that was deemed statistically significant.

Subsequently others improved, however they were not deemed statistically significant.

 

[chinup]

Not sure if they will be doing clinical trials in Japan or anywhere else in the world.

Maybe they could just use USA clinical trials data instead of having to conduct their own clinical trials to get FX-322 approved in those countries. I hope this is the case.

Yeah this should be explored. If they can get approval in Japan quicker than in the US I'm sure many of us will gladly travel overseas and pay quite a bit of money for the therapy.

Not sure how that would affect their business model though, unfortunately this isn't a charity.

 

[Diesel]

You can also have no hearing loss, but still have tinnitus caused by other factors. From what I can observe this doesn't mean that this then is something more complicated necessarily but rather it is possibly caused by something other than just sudden hearing loss for example.

Examples include the fact that people have tinnitus possibly due to synaptic issues for example.

I actually recall a study from a while ago, I'm trying to find it, but it must be on my old computer. It showed audiograms (normal + HF) of various age groups, 18-29, 30-39, 40-49, up to 80s. And it also identified a YES/NO for folks who complained of tinnitus. They provided an average audiogram + HF for the YES/NO tinnitus group. Just for fun, I graphed the points to better understand the data, which I did save:

Vertical axis = Average threshold for the entire group. Horizontal = Audiogram tone tested.

One take-away I had was that it was obvious that the group that had reported having tinnitus had a steeper negative slope as their hearing was tested along the audiogram, and at least 10 dB more loss than the non-tinnitus group.

This is why I think that FX-322 restoring even partial signal for those experiencing tinnitus, just to get them up maybe 10-20 dB on the audiogram per frequency band might be enough to start resolving it. We know from the Phase 1/2, that at the edge of the testing scale, a few patients saw a 10-15 dB improvement at 8 kHz. If their audiograms looked anything like the one above, from 8 kHz + where they saw a 10-15 dB improvement, it might put them into a non-tinnitus range.

 

[Philip83]

Has there been any deeper discussion whether the restoring of hair cells and synapses could potentially worsen hyperacusis/noxacusis? What are the arguments for/against?

 

[frpp]

Yeah this should be explored. If they can get approval in Japan quicker than in the US I'm sure many of us will gladly travel overseas and pay quite a bit of money for the therapy.

Not sure how that would affect their business model though, unfortunately this isn't a charity.

If Japan got it before the U.S. did, I'd be there faster than the flash, Usain Bolt, Superman, and Nightcrawler combined.

 

[Street Novelist]

The full readout is in May, not July. Right?

 

[Lucifer]

The full readout is in May, not July. Right?

Yes, near the end of May for up to Day 210 results. We get results up to Day 90 at the beginning of April.

 

[Diesel]

Has there been any deeper discussion whether the restoring of hair cells and synapses could potentially worsen hyperacusis/noxacusis? What are the arguments for/against?

If FX-322 caused a worsening in hyperacusis or noxacusis, they would have certainly suspended one of the trials by now. That type of outcome would certainly fall into an adverse event category.

 

[FGG]

Has there been any deeper discussion whether the restoring of hair cells and synapses could potentially worsen hyperacusis/noxacusis? What are the arguments for/against?

Noxacusis involves different synapses (type 2 afferent neurons, which are pain fibers, and their synapses on the OHC). I don't see how this drug would make that worse, personally.

 

[FGG]

I actually recall a study from a while ago, I'm trying to find it, but it must be on my old computer. It showed audiograms (normal + HF) of various age groups, 18-29, 30-39, 40-49, up to 80s. And it also identified a YES/NO for folks who complained of tinnitus. They provided an average audiogram + HF for the YES/NO tinnitus group. Just for fun, I graphed the points to better understand the data, which I did save:

View attachment 42284

Vertical axis = Average threshold for the entire group. Horizontal = Audiogram tone tested.

One take-away I had was that it was obvious that the group that had reported having tinnitus had a steeper negative slope as their hearing was tested along the audiogram, and at least 10 dB more loss than the non-tinnitus group.

This is why I think that FX-322 restoring even partial signal for those experiencing tinnitus, just to get them up maybe 10-20 dB on the audiogram per frequency band might be enough to start resolving it. We know from the Phase 1/2, that at the edge of the testing scale, a few patients saw a 10-15 dB improvement at 8 kHz. If their audiograms looked anything like the one above, from 8 kHz + where they saw a 10-15 dB improvement, it might put them into a non-tinnitus range.

I love "just for fun" graphs. Subscribe.

 

[Lucifer]

If Japan got it before the U.S. did, I'd be there faster than the flash, Usain Bolt, Superman, and Nightcrawler combined.

How would it work for other countries outside the USA? Would Astellas Pharma contact countries outside USA once their trials are done and apply to get FX-322 approved in those countries?

I'm just wondering how the process normally works. I don't want a big delay where it's going to be 1-2 years to get released outside USA. Could the delay be similar to the coronavirus vaccine? I know USA and UK got the vaccine this month and for New Zealand it will be delayed till March.

 

[Diesel]

How would it work for other countries outside the USA? Would Astellas Pharma contact countries outside USA once their trials are done and apply to get FX-322 approved in those countries?

I'm just wondering how the process normally works.

Yes. It varies a bit by country, but generally there is a "Drug Approval" process for each region or country. Most, if not all, at this point accept US-FDA Approved trial data for their applications. Some countries' drug-regulating entities require at least part of the trial be conducted on their soil; so Astellas may have to strategically position some Phase 3 trials within specific countries. It also seems like US-FDA trial data and approvals are acceptable to apply to setup Phase 3 trial sites in those countries.

 

[Lucifer]

Yes. It varies a bit by country, but generally there is a "Drug Approval" process for each region or country. Most, if not all, at this point accept US-FDA Approved trial data for their applications. Some countries' drug-regulating entities require at least part of the trial be conducted on their soil; so Astellas may have to strategically position some Phase 3 trials within specific countries. It also seems like US-FDA trial data and approvals are acceptable to apply to setup Phase 3 trial sites in those countries.

I just hope when the pivotal phase is done or during the phase, Astellas Pharma will apply for approval of FX-322 in all countries. Is it possible for them to apply for approval in advance during the pivotal phase if they start noticing the results are positive?

 

[Lucifer]

Has there been any deeper discussion whether the restoring of hair cells and synapses could potentially worsen hyperacusis/noxacusis? What are the arguments for/against?

I don't think it will make hyperacusis/noxacusis worse. There's a better chance for it to improve hyperacusis/noxacusis. I have a good feeling once we restore hearing input then it should stop both loudness and pain hyperacusis.

I think when we loss hair cells due to loud noise it caused hyperacusis to happen and once we restore it should be gone.

I still believe both loudness and pain hyperacusis are happening in the same area.

I suffer from both pain and loudness hyperacusis and I have hope that FX-322 will cure it.

 

[Joe72]

I actually recall a study from a while ago, I'm trying to find it, but it must be on my old computer. It showed audiograms (normal + HF) of various age groups, 18-29, 30-39, 40-49, up to 80s. And it also identified a YES/NO for folks who complained of tinnitus. They provided an average audiogram + HF for the YES/NO tinnitus group. Just for fun, I graphed the points to better understand the data, which I did save:

[their hearing was tested along the audiogram, and at least 10 dB more loss than the non-tinnitus group.

This is why I think that FX-322 restoring even partial signal for those experiencing tinnitus, just to get them up maybe 10-20 dB on the audiogram per frequency band might be enough to start resolving it. We know from the Phase 1/2, that at the edge of the testing scale, a few patients saw a 10-15 dB improvement at 8 kHz. If their audiograms looked anything like the one above, from 8 kHz + where they saw a 10-15 dB improvement, it might put them into a non-tinnitus range.

This theory of yours seems entirely plausible. Prior to November 2020, for the last 6 years or so, I had what I would call a "quiet" high pitched tinnitus on my left side where I would not notice it unless I was specifically listening for it and the room was VERY quiet. I could increase the tinnitus just by clenching my teeth together. That's how I could gauge how bad it was - I would compare clenching teeth to no clenching of teeth, and would always be satisfied that the tinnitus was still the same "quiet" volume in my head. Entirely manageable and not intrusive at all.

Well, about a month ago I experienced a loud traumatic event - my ears felt full for 3 or 4 days, I thought I came down with a sinus infection or something. I had no idea the fullness in my ear, the dampening of all sounds was related to hearing loss. Boy, was I in for a nice surprise about 4 to 7 days later... I can't be sure of the timeline... it just started up late one night and has not gone away... now I have it in BOTH ears, about 2x louder than before and ALWAYS noticeable, even when talking... it's driving me up the wall. Now it's the SAME loudness as when I clench my teeth, but at a slightly different frequency (that's the only way I can tell the sounds apart). I have to literally always be doing something, which is exhausting, in order to try and forget about it. Thoughts of hanging myself now cross my mind, it's torture. On a scale of 1 to 10 prior to the loud event, the tinnitus was perhaps a 1, maybe 2 out of 10. Now it's in the 6 to 7 range of severity, as it has crossed over to both ears, with varying frequency and intensity and I can always hear it.

Perhaps there are some interesting points I can make about my particular case. I lost some high frequency hair cells in my teens from listening to headphones and hard rock too much. I remember my ears would feel hot and numb for 20 minutes or so after listening for prolonged periods (45 minutes to 1 hour). I never had any tinnitus (yet).

Then as I grew older my stress levels increased and I didn't sleep very well - my sleep/wake cycles were all messed up for nearly a decade. I didn't listen to headphones as much anymore, BUT I took dance lessons for years, and wore ear plugs for perhaps 70% of the time (when I remembered them) - the other 30% of the time I would take some chewing gum and stick it in my ears so they didn't hurt. Hard to find earplugs at 1am.

Thinking back to when I was a child my ears were always super sensitive to loud sounds... the school bell would make my ears hurt and I would have to cover my ears. I was born premature by 4 weeks. Already seem to be setting myself up for tinnitus while in an incubator in the 1970's.

Fast forward to my mid-forties (2015) and tinnitus starts to creep into my left ear. I am now careful to wear earplugs everywhere I go - theme park, concerts, outdoor events with big speakers... I had to wear earplugs around my children as well. Ear plugs at the local park. I could not take the pain of loud sounds - anything over 90 dB (I measured it) and it's as if my hearing clipped and plugged up. Hyperacusis? I guess so. I've had it for so long, I actually thought it was normal for everyone to feel the pain of loud sounds. Boy was I stupid. I never asked anyone about it.

Fast forward to November 2020, all it took was ONE loud event, no ear plugs, and boom... my auditory system gets taken over the edge... almost like a cytokine storm... Now what's very interesting is that the loud event was very low frequency... enough to shock the cilia in my ears... so it most likely killed cilia that were already on the verge of dying within the next 10 years... but this noise just accelerated their death... that's what I think. Or I just ended up killing more hair fibers. Can fibers partially work? Who knows.

The way I see it - since I already had some hearing loss... regardless of how little... plus mild tinnitus already... plus the added stresses in life... plus a poor diet and lack of exercise... I basically set my neurological system up for failure... it was not resilient enough to cope with adverse auditory events. I also suffered from joint pains, 10 year old injuries would still hurt, small injuries would take forever to heal or not heal at all, and nobody could figure out why. Medical establishment was useless. I suffered pains all over my body.

I bet restoring even a few of my missing hair cells would reduce the tinnitus back to some manageable level... I will take 10% to 20% reduction any day over nothing. When I look at that graph you posted, I see myself in the red line... and I believe I can get back to the green line. That would be a miracle. I would cut off my little finger if that's all it took.

 

[serendipity1996]

I don't think it will make hyperacusis/noxacusis worse. There's a better chance for it to improve hyperacusis/noxacusis. I have a good feeling once we restore hearing input then it should stop both loudness and pain hyperacusis.

I think when we loss hair cells due to loud noise it caused hyperacusis to happen and once we restore it should be gone.

I still believe both loudness and pain hyperacusis are happening in the same area.

I suffer from both pain and loudness hyperacusis and I have hope that FX-322 will cure it.

I'm inclined to agree - although noxacusis is a bit of an unknown generally-one thing we do know is that noxacusis/hyperacusis arises as a consequence of peripheral damage and hearing loss. So restoring input via FX-322 shouldn't worsen it at all IMO even if, for example, it doesn't necessarily improve it either.