Frequency Therapeutics — Hearing Loss Regeneration

[katri]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

 

[Princebeyel]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

I know for me personally restoring hearing would help me with my tinnitus as in the morning, until I put my hearing aids in, my tinnitus is extremely bad and noticeable.

 

[Bill Arsenault]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

Hey Katri.

Don't be surprised that the "Men" around here would leave a lady waiting.

They are all clearly impotent.

 

[Zugzug]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

I'll save you a lot of time and let the geniuses of the thread rest their backs after carrying it so hard.

The general consensus on this forum is that for noise-induced tinnitus and hyperacusis (particularly loudness hyperacusis, as noxacusis has more unknowns), the combination of FX-322 (repairs hair cells with newly formed synapses) and OTO-413 (repairs synapses) should, at the very least, make a difference. We are awaiting results for FX-322 Phase 2a; the Phase 1/2 for both drugs is promising. Many people are hoping the results are strong enough for the process to speed up via Breakthrough Therapy designation.

The more the cause deviates from noise-induced, the more unknowns. It's not because it can't help other causes as well, but rather that it's a lot more obvious what is happening when someone experiences noise trauma. If I sound like an idiot, one of the geniuses can correct me.

 

[Jrblovsky]

This is actually something I have been pondering myself, and it's something I don't see often discussed here on Tinnitus Talk. I also find this as one of the most stressful things about experiencing these symptoms; have I had this all my life and am only just now finding it problematic? I suppose it could be the case that my sudden awareness is manifesting as a spike. It really makes me wonder how much of this is psychological.

I know that "true silence" isn't actually possible outside of the vacuum of space, but I am curious how those without tinnitus can hear nothing in a quiet place. I haven't bothered asking unafflicted friends and family to try this in fear that they will hear something and not let it go...

I heard pure silence in dead quiet before this hell. I think that is one of the reasons why I am so severely affected by tinnitus. One year in and I still can't stand it.

 

[Drachen]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

I am relatively new to researching into this subject, but here is my take from all that I've gathered.

FX-322 would work with tinnitus is a result of restoration of hearing cells that were damaged or killed by noise exposure. The idea is that if the hairs are restored, as well as the connections between them and the brain, there is no longer a need for the overcompensation that occurs.

Of course, it is still true that tinnitus is a very complex symptom that can be caused and exacerbated by many things. It does, however, seem logical that if you have noise-induced hearing loss and it was your primary cause of tinnitus, restoration of hearing would let the brain know that it's okay to chill out.

@FGG and others have written previously far more detailed and scientific explanations that might better answer your question, but I think I am on track here.

 

[AfroSnowman]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

The theory is that most tinnitus is connected to/caused by hearing loss. The cited proof of this theory is a significant number of people reporting a reduction or elimination of tinnitus when using hearing aids. Alternatively most people without tinnitus put in a truly silent environment will start to experience tinnitus. This all suggests that when the damaged parts of our auditory system start to produce input again the tinnitus will reduce or I guess disappear.

I have severe intrusive tinnitus, if the restoration of some of the of my hearing could make the tinnitus maskable or unnoticeable in loud environments that would be a true life changing Godsend.

Will FX-322 do it? We just have to be patient and hopeful. Hopefully we will get a real hint in March.

 

[Diesel]

Do you guys actually think FX-322 can help people with severe/intrusive tinnitus? And in what ways exactly?

I'd like to add that Carl LeBel from Frequency Therapeutics himself also said on the Tinnitus Talk Podcast that some participants of the FX-322 Phase 1/2 noticed improvements in their tinnitus.

Now, they're measuring for tinnitus improvement in the FX-322 Phase 2A, and two other Phase 1B trials.

So don't just take our words for it, even Frequency Therapeutics seems confident that the drug will treat tinnitus in a positive way.

With that said there was an anecdote from a Phase 2A participant that their tinnitus improved also, and so did their hearing. But, we don't have any specifics.

I think we'll know more about the results of the ability of FX-322 to treat tinnitus in Q1 of 2021.

When it comes to people who have Acquired SNHL (noise induced, or others) and also experience tinnitus as a symptom of the condition; the general consensus is fairly straightforward:

The tinnitus in this condition is likely experienced from the damage or death of sensory hair cells in the cochlea. The brain is generating the tinnitus sound because it isn't getting enough of a signal from those sensory cells. For many, if they experience new damage to their ears, they notice the tinnitus gets worse in some way.

Less good sensory hair cells = more tinnitus experienced.

Therefore, FX-322 activating the growth of brand new sensory hair cells, and those new hair cells providing a useful signal to the brain, should result in reduced tinnitus.

 

[Drachen]

Now, they're measuring for tinnitus improvement in the FX-322 Phase 2A, and two other Phase 1B trials.

Though I was hesitant to do this before, I must ask: why are they not also pushing the fact that this could have considerable benefits as it comes to treatment of tinnitus?

As far as I can tell, FX-322 is being presented solely as a treatment for sensorineural hearing loss. While it's true tinnitus comes in many shapes and sizes, they could still be promoting the idea it may also treat tinnitus caused by hearing loss. You might say they don't know that it would for sure, but that also applies to their primary claim of its efficacy for restoring hearing in general.

My skeptical side is wondering if this is because they don't believe it will have much of an effect. As they have a more intimate knowledge of the specifics of the drug, do they have feelings it won't be as effective as hoped? There is the possibility they might revise their marketing strategy to involve more frequent mentions of tinnitus following clinically significant improvements in the next phase, but given the further appeal this drug would have, it seems like it would be a good bet to start with that now.

Perhaps I am overthinking this. There is also a chance I have missed media that would otherwise show they are indeed talking about its potential service as a treatment for tinnitus. Please inform me if I have missed anything.

 

[FGG]

Though I was hesitant to do this before, I must ask: why are they not also pushing the fact that this could have considerable benefits as it comes to treatment of tinnitus?

As far as I can tell, FX-322 is being presented solely as a treatment for sensorineural hearing loss. While it's true tinnitus comes in many shapes and sizes, they could still be promoting the idea it may also treat tinnitus caused by hearing loss. You might say they don't know that it would for sure, but that also applies to their primary claim of its efficacy for restoring hearing in general.

My skeptical side is wondering if this is because they don't believe it will have much of an effect. As they have a more intimate knowledge of the specifics of the drug, do they have feelings it won't be as effective as hoped? There is the possibility they might revise their marketing strategy to involve more frequent mentions of tinnitus following clinically significant improvements in the next phase, but given the further appeal this drug would have, it seems like it would be a good bet to start with that now.

Perhaps I am overthinking this. There is also a chance I have missed media that would otherwise show they are indeed talking about its potential service as a treatment for tinnitus. Please inform me if I have missed anything.

They started the trial as a hearing loss drug and that's what they are seeking FDA approval for.

During Phase 1, they received anecdotal evidence from the testing sites that it also helped tinnitus. These must have been at least reasonably strong anecdotes because they weren't testing for it in Phase 1 but the investigators offered to them that their subjects were reporting this unprompted. Now tinnitus is added as a measure to the current phase.

It doesn't make sense for them to promote it before they have the hard numbers. They will have those spring 2021.

 

[FGG]

Hey Katri.

Don't be surprised that the "Men" around here would leave a lady waiting.

They are all clearly impotent.

I, for one, am not a man .

 

[Danad]

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.

I am revisiting @Diesel's post regarding the audiogram differences between having tinnitus and not. This is, I believe, a pivotal finding. His chart may have answered a question I previously posited on this forum:

"The evidence overwhelmingly points to tinnitus as a maladaptive manifestation occurring within the audio processing areas of the brain due to reduced or corrupted audio input. The question here is what degree of hearing restoration is necessary to reverse this process and will FX-322 provide that."​

The data suggests only 10-15 dB improvement may be necessary to suppress tinnitus... very promising news indeed since FX-322 has demonstrated this capability.

 

[GBB]

I, for one, am not a man .

 

[GlennS]

There is also a chance I have missed media that would otherwise show they are indeed talking about its potential service as a treatment for tinnitus.

Yes you did, namely an interview between them and Tinnitus Talk.

 

[Drachen]

These must have been at least reasonably strong anecdotes because they weren't testing for it in Phase 1 but the investigators offered to them that their subjects were reporting this unprompted. Now tinnitus is added as a measure to the current phase.

Ah, thank you. This actually does sound optimistic if what they heard was enough to have them pivot from their original plans.

I suppose at this point it's a long waiting game until Spring.

Yes you did, namely an interview between them and Tinnitus Talk.

Thank you! I had the opportunity to look over the transcript a bit. As I am still new here, there's a lot I have to find out about the resources and such available.

 

[Diesel]

I am revisiting @Diesel's post regarding the audiogram differences between having tinnitus and not. This is, I believe, a pivotal finding. His chart may have answered a question I previously posited on this forum:

"The evidence overwhelmingly points to tinnitus as a maladaptive manifestation occurring within the audio processing areas of the brain due to reduced or corrupted audio input. The question here is what degree of hearing restoration is necessary to reverse this process and will FX-322 provide that."​

The data suggests only 10-15 dB improvement may be necessary to suppress tinnitus... very promising news indeed since FX-322 has demonstrated this capability.

I will be interested to see how patients' TFI scores changed from FX-322 treatment; especially with multiple doses, hopefully going deeper into the cochlea.

Tinnitus specifically as a symptom of Acquired SNHL is poorly measured and understood as it is. The TFI is a good starting point, but doesn't actually give specifics on the patients description of the tinnitus they are experiencing.

Considering what I have read from anecdotes on this site, the perception of tinnitus is all over the place: static, buzzing, high/mid/low frequency pure tones, hums, crickets, etc. My assumption, based on personal experience, is the tinnitus is somehow related to some hearing loss in that specific location for most people.

When I think about these responses, and my own situation, I consider where in the frequency range these sounds exist, and the likelihood that someone with similarly described tinnitus received FX-322 in the Phase 2A.

In my opinion, it's highly probable that the lower in frequency the tinnitus, the more doses (assuming they get deeper) will be required to reach the affected area.

I am hopeful that if the tinnitus of the patient is generally in a higher frequency that FX-322 can treat, we should see a significant drop in TFI score.

What gives me pause are the folks that have multiple tones, or tinnitus that matches to sounds that are lower frequencies. For example, a hum or buzzing or crickets might spread well below 4 kHz.

So, what if someone saw just part of that tinnitus sound go away/get quieter but some remained? Would the drop in TFI be significant?

Or, perhaps the amount of healthy cells above that affected range is providing enough signal to quiet down remaining midrange damage? How would that affect a TFI score?

 

[Diesel]

Another reason that I think FX-322 will help improve tinnitus, depending on where it is.

Tinnitus with a Normal Audiogram

I have continuously been suspect that there SHOULD BE a correlation between audiogram performance and tinnitus. Many, myself included have "normal" audiograms, but still have tinnitus. I have suspected, as this article shows, that the audiogram isn't detailed enough to show the specific location of the losses. Whether, it's on the "normal" range or "high-frequency."

Restoring those "niche" or "detailed" areas where we have tinnitus due to substantially damaged cells, even if it's 10-20 dB, may be enough to begin noticing an improvement.

 

[Philip83]

Another reason that I think FX-322 will help improve tinnitus, depending on where it is.

Tinnitus with a Normal Audiogram

I have continuously been suspect that there SHOULD BE a correlation between audiogram performance and tinnitus. Many, myself included have "normal" audiograms, but still have tinnitus. I have suspected, as this article shows, that the audiogram isn't detailed enough to show the specific location of the losses. Whether, it's on the "normal" range or "high-frequency."

Restoring those "niche" or "detailed" areas where we have tinnitus due to substantially damaged cells, even if it's 10-20 dB, may be enough to begin noticing an improvement.

Agreed. Audiograms are extremely blunt in their application, especially when monitoring such a complex system as the ear/hearing.

 

[twa]

Another reason that I think FX-322 will help improve tinnitus, depending on where it is.

Tinnitus with a Normal Audiogram

I have continuously been suspect that there SHOULD BE a correlation between audiogram performance and tinnitus. Many, myself included have "normal" audiograms, but still have tinnitus. I have suspected, as this article shows, that the audiogram isn't detailed enough to show the specific location of the losses. Whether, it's on the "normal" range or "high-frequency."

Restoring those "niche" or "detailed" areas where we have tinnitus due to substantially damaged cells, even if it's 10-20 dB, may be enough to begin noticing an improvement.

I have this, a normal audiogram but a dip from 6000 Hz - 8000 Hz to almost 20 dB. Technically, it is still considered normal by two doctors. One considers the dip enough to set off tinnitus. Interestingly enough, my Dad has hearing loss but didn't notice tinnitus until I asked him about it. He said he had some hearing loss at 19 when he took a hearing test in the Air Force.

 

[twa]

Though I was hesitant to do this before, I must ask: why are they not also pushing the fact that this could have considerable benefits as it comes to treatment of tinnitus?

As far as I can tell, FX-322 is being presented solely as a treatment for sensorineural hearing loss. While it's true tinnitus comes in many shapes and sizes, they could still be promoting the idea it may also treat tinnitus caused by hearing loss. You might say they don't know that it would for sure, but that also applies to their primary claim of its efficacy for restoring hearing in general.

My skeptical side is wondering if this is because they don't believe it will have much of an effect. As they have a more intimate knowledge of the specifics of the drug, do they have feelings it won't be as effective as hoped? There is the possibility they might revise their marketing strategy to involve more frequent mentions of tinnitus following clinically significant improvements in the next phase, but given the further appeal this drug would have, it seems like it would be a good bet to start with that now.

Perhaps I am overthinking this. There is also a chance I have missed media that would otherwise show they are indeed talking about its potential service as a treatment for tinnitus. Please inform me if I have missed anything.

I think it's because they have bigger fish to fry. Tinnitus is a very big problem for us, but for the world in general hearing loss is more incapacitating. If they can produce an effective treatment for hearing loss primarily, tinnitus remission is gravy. As tinnitus sufferers we know there would be a market for a tinnitus treatment, but from a medical point of view they are going for the brass ring.

 

[Drachen]

I think it's because they have bigger fish to fry.

Yeah, I think you and the others are right here. It's best to just focus on what your main goal is and work from excellent results that are sure to follow in this next phase.

When viewing the more tinnitus-focused objectives such as the Lenire device, the Dr. Shore device, and the Hough Ear Institute Pill, all of which seem to be in questionable waters right now, I really would like to see something for the tinnitus crowd.

If there are steep TFI reductions after reviewing this next batch of candidates, it would be great if they started making a big deal out of that as well.

 

[Lucifer]

Yeah, I think you and the others are right here. It's best to just focus on what your main goal is and work from excellent results that are sure to follow in this next phase.

When viewing the more tinnitus-focused objectives such as the Lenire device, the Dr. Shore device, and the Hough Ear Institute Pill, all of which seem to be in questionable waters right now, I really would like to see something for the tinnitus crowd.

If there are steep TFI reductions after reviewing this next batch of candidates, it would be great if they started making a big deal out of that as well.

Advertising is key. If FX-322 does end up passing Phase 2a clinical trials, they have to increase their advertising and let the whole world know that FX-322 works for hearing loss.

 

[Drachen]

If FX-322 does end up passing Phase 2a clinical trials, they have to increase their advertising and let the whole world know that FX-322 works for hearing loss.

I want to see people going wild over this, but it probably is too early. Just to think: this could be the first ever drug of likely many more to come that actually has an effect on hearing loss.

Hearing loss.

We are getting closer and closer to at the very least partially reviving an entire SENSE. It's really hard not to get too excited here. I've already told my grandparents that they could potentially get some of their hearing back with a shot (likely shots). It's incredible.

 

[lymebite]

There is an old saying, which is attributed to Ralph Waldo Emerson:

"Build a better mousetrap, and the world will beat a path to your door."

My hunch is this will be the case with FX-322.

Once the Frequency Therapeutics mousetrap is ready, I think the news will spread like wildfire.

 

[Diesel]

Advertising is key. If FX-322 does end up passing Phase 2a clinical trials, they have to increase their advertising and let the whole world know that FX-322 works for hearing loss.

This is the reason. They don't have concrete data to prove that FX-322 helps tinnitus. If the TFI test used in the Phase 2A shows a significant enough decrease, they will certainly begin adding tinnitus to their marketing communications.

FX-322 is PRIMARILY intended to be a hearing loss regeneration drug. So, those end-points directly related to hearing loss will be the ones most important to the FDA. Audiogram, Word-in-Quiet, Word-in-Noise.

These secondary outcomes, Tinnitus Functional Index, Quality of Life, Extended-High-Frequency Audiogram still matter.

A drug that reduces tinnitus symptoms (by restoring hearing) still has a market of millions of people just in the US. How many people here have "normal" hearing, but noise-induced, high-frequency tinnitus? Right now there is nothing for that population. Still matters; but not the primary outcome to the FDA.

After the Phase 1/2 data was released; Frequency Therapeutics started more marketing communications re: general hearing loss, word-recognition, and hearing-in-noise challenges. They have data that shows positive outcomes in those areas. If more of the secondary outcomes look good from the Phase 2A, they'll definitely add it to their messaging immediately.

 

[tommyd87]

This is the reason. They don't have concrete data to prove that FX-322 helps tinnitus. If the TFI test used in the Phase 2A shows a significant enough decrease, they will certainly begin adding tinnitus to their marketing communications.

FX-322 is PRIMARILY intended to be a hearing loss regeneration drug. So, those end-points directly related to hearing loss will be the ones most important to the FDA. Audiogram, Word-in-Quiet, Word-in-Noise.

These secondary outcomes, Tinnitus Functional Index, Quality of Life, Extended-High-Frequency Audiogram still matter.

A drug that reduces tinnitus symptoms (by restoring hearing) still has a market of millions of people just in the US. How many people here have "normal" hearing, but noise-induced, high-frequency tinnitus? Right now there is nothing for that population. Still matters; but not the primary outcome to the FDA.

After the Phase 1/2 data was released; Frequency Therapeutics started more marketing communications re: general hearing loss, word-recognition, and hearing-in-noise challenges. They have data that shows positive outcomes in those areas. If more of the secondary outcomes look good from the Phase 2A, they'll definitely add it to their messaging immediately.

The only issue is that we don't know that high frequency tinnitus is caused by noise induced hearing loss of the type that will be treated utilising FX-322. If this is the case then I agree that the treatment will work well with this population and as a result there will be a bigger and better outcome with FX-322. My view is that before Frequency Therapeutics can certainly claim that FX-322 works with treating tinnitus, they need to establish what the cause of tinnitus is conclusively because it could be possible that they treat people with very high frequency hearing loss but do not fully resolve tinnitus.

Thus I think that the reality will be that even if FX-322 does benefit tinnitus (this seems reasonably probable), I can still see them acting with some caution around their tinnitus commentary to avoid making unconfirmed or challengeable claims about FX-322.

I think it's because they have bigger fish to fry. Tinnitus is a very big problem for us, but for the world in general hearing loss is more incapacitating. If they can produce an effective treatment for hearing loss primarily, tinnitus remission is gravy. As tinnitus sufferers we know there would be a market for a tinnitus treatment, but from a medical point of view they are going for the brass ring.

This is what I agree with. What I reckon is if FX-322 treats hearing loss, and if it ends up being shown to be the underlying cause(s) of tinnitus, then it will result in a bigger benefit.

Basically I think that this view might be unpopular to some here (and I personally want the tinnitus gone also) because a large proportion of those with both hearing loss and tinnitus tend to prefer treating the hearing loss first before tinnitus, if they need to select one of these.

 

[twa]

I want to see people going wild over this, but it probably is too early. Just to think: this could be the first ever drug of likely many more to come that actually has an effect on hearing loss.

Hearing loss.

We are getting closer and closer to at the very least partially reviving an entire SENSE. It's really hard not to get too excited here. I've already told my grandparents that they could potentially get some of their hearing back with a shot (likely shots). It's incredible.

I said the same thing to my 80-year-old father and he said it probably won't be ready in time for him. I wish it was, he has hearing loss and it is hard to communicate with him between his hearing loss and my hyperacusis. Can you imagine? He is yelling and I'm holding my ears!

 

[Diesel]

Thus I think that the reality will be that even if FX-322 does benefit tinnitus (this seems reasonably probable), I can still see them acting with some caution around their tinnitus commentary to avoid making unconfirmed or challengeable claims about FX-322.

If I understand correctly, I agree that they won't come out and make a blanket claim that FX-322 treats tinnitus. Meaning, tinnitus in the broad sense of "ringing in the ears," without disclosing the cause.

They may however begin to comment on how noise-induced hearing loss sometimes also causes tinnitus.

They may also be able to draw specific correlations between their data, which if statistically significant, they can make more specific claims to FX-322 treating tinnitus as a symptom of hearing loss. Or treating hearing loss, or tinnitus and thereby improving quality of life.

For example, if significant:

Overall significant improvements in primary endpoints positively correlate with a reduction in TFI score, and increase in QOL measure.

A stepped improvement in primary endpoints and stepped reduction in QOL measure. For example: 1 dose population saw an average of 7 point TFI reduction, 2 dose: 14 point, 4 dose: 28 point.

With this type of data, if statistically significant, it provides enough evidence that regenerating inner and outer hair cells is connected to treating tinnitus when the condition is acquired SNHL. At that point, they can make certain claims.

I can certainly see the general public thinking, "oh yay this will fix my tinnitus" and they will need to consult their doctor at that point to understand whether their tinnitus is a symptom of SNHL or something else.

 

[Lucifer]

I said the same thing to my 80-year-old father and he said it probably won't be ready in time for him. I wish it was, he has hearing loss and it is hard to communicate with him between his hearing loss and my hyperacusis. Can you imagine? He is yelling and I'm holding my ears!

Who would have thought that by being exposed to loud noise we would have gotten tinnitus and hyperacusis. The only thing we knew about loud noise is that it can cause hearing loss, but tinnitus and hyperacusis... I had no idea these conditions even existed.

 

[FGG]

If I understand correctly, I agree that they won't come out and make a blanket claim that FX-322 treats tinnitus. Meaning, tinnitus in the broad sense of "ringing in the ears," without disclosing the cause.

They may however begin to comment on how noise-induced hearing loss sometimes also causes tinnitus.

They may also be able to draw specific correlations between their data, which if statistically significant, they can make more specific claims to FX-322 treating tinnitus as a symptom of hearing loss. Or treating hearing loss, or tinnitus and thereby improving quality of life.

For example, if significant:

Overall significant improvements in primary endpoints positively correlate with a reduction in TFI score, and increase in QOL measure.

A stepped improvement in primary endpoints and stepped reduction in QOL measure. For example: 1 dose population saw an average of 7 point TFI reduction, 2 dose: 14 point, 4 dose: 28 point.

With this type of data, if statistically significant, it provides enough evidence that regenerating inner and outer hair cells is connected to treating tinnitus when the condition is acquired SNHL. At that point, they can make certain claims.

I can certainly see the general public thinking, "oh yay this will fix my tinnitus" and they will need to consult their doctor at that point to understand whether their tinnitus is a symptom of SNHL or something else.

This is a really good point.

If they market it for tinnitus more generally, people who have other causes (apart from hair cell damage) will be potentially misled by the promise of a "tinnitus treatment" that wouldn't benefit people who have: middle ear disease, ETD, TMJ, iron deficiency, hydrops without hair cell loss, etc. It would be up to the ENTs and audiologists to do a better job determining the cause and educating people but I also think the marketing of this needs to be very specific.