Frequency Therapeutics — Hearing Loss Regeneration

[Danad]

This can happen for any drug, not just the ones which are designated as a breakthrough therapy?

While I hope this happens, I'm a little concerned with the drug not reaching into the lower frequencies. While I strongly believe it should be approved even if it only affects frequencies that are > 6-8kHz, conventional practice (as well as audiograms) tend to only see those lower frequencies as important.

Ideally the drug will show to be more effective during phase 2, or at least all of the people who are in charge of early approval will realize that restoring the higher frequencies is actually more important for millions of individuals.

Personally I think healing those higher frequencies will actually fix tinnitus for more people than healing the lower ones. The fact that this drug isn't being tested primarily for tinnitus-related efficacy is what has me worried.

I would not worry about Frequency Therapeutics not testing for tinnitus-related efficacy, with such a varied etiology I believe adding tinnitus would complicate their clinical studies needlessly. Expanding their market with a supplemental indication will be easier once FX-322 is approved for hearing loss... which most tinnitus patients have anyway.

 

[Jack V]

This can happen for any drug, not just the ones which are designated as a breakthrough therapy?

I believe so.

While I hope this happens, I'm a little concerned with the drug not reaching into the lower frequencies. While I strongly believe it should be approved even if it only affects frequencies that are > 6-8kHz, conventional practice (as well as audiograms) tend to only see those lower frequencies as important.

Ideally the drug will show to be more effective during phase 2, or at least all of the people who are in charge of early approval will realize that restoring the higher frequencies is actually more important for millions of individuals.

Personally I think healing those higher frequencies will actually fix tinnitus for more people than healing the lower ones. The fact that this drug isn't being tested primarily for tinnitus-related efficacy is what has me worried.

Doesn't worry me at all. Here's why, as I understand it...

Drug companies may view many potential uses, and therefore many potential income streams, for a drug under development. Therefore, going into initial clinical trials, they have to make a strategic decision. If they test broadly for multiple conditions and receive broad FDA approval, they can maximize profits. At the same time, if the drug proves effective for some conditions but not all, and they don't receive FDA approval, they have to refine their trials and start from scratch. In other words, if the company gets over-confident and greedy, their trials could flame out and the drug gets delayed.

On the other hand, if their initial trial is limited, designed for the lowest hanging fruit, the condition easiest to prove, then they maximize potential for earliest approval. With the drug on the market, they can then run additional trials for additional conditions and receive additional approvals if those trials are also successful.

Why I'm not worried that the drug isn't being tested primarily for tinnitus-related efficacy, is that once it's approved for any condition, it's available off-label any way your doctor wants to prescribe it. Therefore, assuming it helps tinnitus, the path of least resistance may be to establish efficacy for another condition that's easier to prove first, bringing it to market -- bringing it to us -- as fast as possible.

The company could then follow up with additional trials for tinnitus that, if approved, makes it reimbursable, but if not approved (if not effective to FDA standards, but still helpful to some subset of tinnitus sufferers), doesn't remove the drug from the market.

 

[Jack V]

I would not worry about Frequency Therapeutics not testing for tinnitus-related efficacy, with such a varied etiology I believe adding tinnitus would complicate their clinical studies needlessly. Expanding their market with a supplemental indication will be easier once FX-322 is approved for hearing loss... which most tinnitus patients have anyway.

Didn't see your response until after I posted mine. I believe we're saying the same thing, although you're saying it more succinctly!

 

[AtlasFainted]

I for one support tinnitus-related efficacy not being a primary outcome of the study. Too much subjectivity; too many unknowns about the cause of tinnitus. Restoring hearing using common and accepted metrics by clinicians is the better metric to get FX-322 to the market effectively; and based on the Phase 1/2, it looks promising.

One thing I think we can know for nearly certain is that FX-322 didn't make tinnitus worse for any patients during the Phase 1/2. If tinnitus worsened for only a handful of participants, the FDA would not have considered it safe, and would not have allowed Frequency to continue to a Phase 2a.

The two outcomes I will be looking for on the Phase 2a are extended audiogram improvements (8kHz - 16kHz), and a reduction in Tinnitus Functional Index by participants that received FX-322. If these two show improvements at significant levels, then it stands to reason that restoring hair cells reduces tinnitus symptoms for folks with Noise-Induced hearing loss. In my opinion, this discovery would be a groundbreaking finding for folks with tinnitus.

Also... Carl LeBel of Frequency agreeing to join a Tinnitus Talk Podcast sure is telling...

Personally I already believe FX-322 cures tinnitus for noise-induced people who have it in the higher frequencies. There's tons of little indicators of this (such as Frequency agreeing to do the Tinnitus Talk Podcast, as you mentioned).

I also remember there being a soundbyte from a Q&A where someone from Frequency Therapeutics more or less said they have seen evidence that it helps tinnitus, but they said it in a very subtle way that wouldn't potentially get them sued.

My concern is really the FDA not seeing higher frequency regeneration as important/relevant enough where it relates to speech to give FX-322 breakthrough status.

The fact that most of the hearing professional community only uses 0-8kHz audiograms, along with what that implies, is what discourages me a bit.

 

[AtlasFainted]

I would not worry about Frequency Therapeutics not testing for tinnitus-related efficacy, with such a varied etiology I believe adding tinnitus would complicate their clinical studies needlessly. Expanding their market with a supplemental indication will be easier once FX-322 is approved for hearing loss... which most tinnitus patients have anyway.

Yeah I definitely think it will be approved! I also understand what you mean by varied etiology, that is a good point.

How soon is it is approved is the only area I'm worried about. I.e will the FDA see the higher frequencies as important enough to give FX-322 breakthrough status?

 

[AtlasFainted]

I believe so.

Doesn't worry me at all. Here's why, as I understand it...

Drug companies may view many potential uses, and therefore many potential income streams, for a drug under development. Therefore, going into initial clinical trials, they have to make a strategic decision. If they test broadly for multiple conditions and receive broad FDA approval, they can maximize profits. At the same time, if the drug proves effective for some conditions but not all, and they don't receive FDA approval, they have to refine their trials and start from scratch. In other words, if the company gets over-confident and greedy, their trials could flame out and the drug gets delayed.

On the other hand, if their initial trial is limited, designed for the lowest hanging fruit, the condition easiest to prove, then they maximize potential for earliest approval. With the drug on the market, they can then run additional trials for additional conditions and receive additional approvals if those trials are also successful.

Why I'm not worried that the drug isn't being tested primarily for tinnitus-related efficacy, is that once it's approved for any condition, it's available off-label any way your doctor wants to prescribe it. Therefore, assuming it helps tinnitus, the path of least resistance may be to establish efficacy for another condition that's easier to prove first, bringing it to market -- bringing it to us -- as fast as possible.

The company could then follow up with additional trials for tinnitus that, if approved, makes it reimbursable, but if not approved (if not effective to FDA standards, but still helpful to some subset of tinnitus sufferers), doesn't remove the drug from the market.

Yeah I agree and I'm aware of this. FX-322 does regenerate hearing and that is what they are basing their efficacy on.

If you are right about Frequency Therapeutics not necessarily needing breakthrough status to get this on the market before phase 3 is completed, that's amazing news.

Most hearing professionals don't seem to understand how important frequencies above 8kHz are.

This made me wonder if regenerating the higher frequencies will be seen as significant enough by the FDA to award breakthrough status.

 

[FGG]

I believe so.

Doesn't worry me at all. Here's why, as I understand it...

Drug companies may view many potential uses, and therefore many potential income streams, for a drug under development. Therefore, going into initial clinical trials, they have to make a strategic decision. If they test broadly for multiple conditions and receive broad FDA approval, they can maximize profits. At the same time, if the drug proves effective for some conditions but not all, and they don't receive FDA approval, they have to refine their trials and start from scratch. In other words, if the company gets over-confident and greedy, their trials could flame out and the drug gets delayed.

On the other hand, if their initial trial is limited, designed for the lowest hanging fruit, the condition easiest to prove, then they maximize potential for earliest approval. With the drug on the market, they can then run additional trials for additional conditions and receive additional approvals if those trials are also successful.

Why I'm not worried that the drug isn't being tested primarily for tinnitus-related efficacy, is that once it's approved for any condition, it's available off-label any way your doctor wants to prescribe it. Therefore, assuming it helps tinnitus, the path of least resistance may be to establish efficacy for another condition that's easier to prove first, bringing it to market -- bringing it to us -- as fast as possible.

The company could then follow up with additional trials for tinnitus that, if approved, makes it reimbursable, but if not approved (if not effective to FDA standards, but still helpful to some subset of tinnitus sufferers), doesn't remove the drug from the market.

Yep. 100% of hearing regeneration drugs will be used off-label. I would bet a good deal of money on this.

 

[serendipity1996]

Personally I already believe FX-322 cures tinnitus for noise-induced people who have it in the higher frequencies. There's tons of little indicators of this (such as Frequency agreeing to do the Tinnitus Talk Podcast, as you mentioned).

I also remember there being a soundbyte from a Q&A where someone from Frequency Therapeutics more or less said they have seen evidence that it helps tinnitus, but they said it in a very subtle way that wouldn't potentially get them sued.

My concern is really the FDA not seeing higher frequency regeneration as important/relevant enough where it relates to speech to give FX-322 breakthrough status.

The fact that most of the hearing professional community only uses 0-8kHz audiograms, along with what that implies, is what discourages me a bit.

I think Frequency has mentioned how the extended higher frequencies also play a role in clarity and there's a fair bit of research which supports this, e.g. I just found this paper 'Extended high-frequency hearing enhances speech perception in noise' (2019) so I think they've got a very good case for breakthrough status.

 

[FGG]

I think Frequency has mentioned how the extended higher frequencies also play a role in clarity and there's a fair bit of research which supports this, e.g. I just found this paper 'Extended high-frequency hearing enhances speech perception in noise' (2019) so I think they've got a very good case for breakthrough status.

You are on fire with uncovering great research papers lately. Props!

 

[serendipity1996]

You are on fire with uncovering great research papers lately. Props!

This is a compliment indeed coming from the queen that is FGG - your contributions to the forum are appreciated by many!

 

[Jack V]

Yep. 100% of hearing regeneration drugs will be used off-label. I would bet a good deal of money on this.

Tinnitus: always the bridesmaid, never the bride

 

[Ten Letter Word]

One thought that's crossed my mind... If FX-322 makes it to market it's going to get a new/real name.

I wonder what they might call it?

As unaffectionate a name FX-322 is, I've definitely grown fond of it It will be weird potentially calling it anything else!

 

[Don Tinny]

I am worried about not seeing more news about this in the mainstream media.

I mean... if we are 2 or 3 years away from regenerating the human ear.

 

[ThomasC]

I think Frequency has mentioned how the extended higher frequencies also play a role in clarity and there's a fair bit of research which supports this, e.g. I just found this paper 'Extended high-frequency hearing enhances speech perception in noise' (2019) so I think they've got a very good case for breakthrough status.

It's just a personnal anecdote, but I have very high frequencies hearing loss and I do struggle with speech clarity in noise. Speech in noise sounds like gibberish to me. People often ask me if I'm deaf, but I'm not. I hear and understand speech 90 % of the time, exept where there is too much noise around me.

 

[Diesel]

I am worried about not seeing more news about this in the mainstream media.

I mean... if we are 2 or 3 years away from regenerating the human ear.

On-going clinical trials don't make for the most interesting news for the mainstream media. It would be really challenging to explain what FX-322 can do right now in a 2-5min news piece.

Results of the trials, especially after the Phase 2a/2b may get more attention. The mainstream media will want news that is concrete to the viewers and can be "sexy-ed" up to get eyeballs. Example: "Breakthrough drug that regenerates human hearing in final clinical stage." Or "FDA gives green light to breakthrough hearing regeneration drug."

 

[Jack V]

On-going clinical trials don't make for the most interesting news for the mainstream media. It would be really challenging to explain what FX-322 can do right now in a 2-5min news piece.

Results of the trials, especially after the Phase 2a/2b may get more attention. The mainstream media will want news that is concrete to the viewers and can be "sexy-ed" up to get eyeballs. Example: "Breakthrough drug that regenerates human hearing in final clinical stage." Or "FDA gives green light to breakthrough hearing regeneration drug."

Or "groundbreaking drug generates 300 page thread from a handful of people on an obscure internet forum"

 

[all to gain]

I am worried about not seeing more news about this in the mainstream media.

I mean... if we are 2 or 3 years away from regenerating the human ear.

And then, knowing our luck, when everybody gets to know about it a 5-year waiting list will appear overnight to get the damn thing...

 

[Diesel]

And then, knowing our luck, when everybody gets to know about it a 5-year waiting list will appear overnight to get the damn thing...

Not likely in the pharma industry; they'll have time and the equipment to ramp up production. If anything you'll have to schedule the ENT visit well in advance. The demand will be on the professionals to administer the drug.

 

[FGG]

And then, knowing our luck, when everybody gets to know about it a 5-year waiting list will appear overnight to get the damn thing...

This has been said here before and probably bears repeating: most ENTs do not do IT injections but all Otologists do. If you can't get a referral to an Otologist, find an ENT who specializes in Meniere's, they are used to doing IT injections.

Don't wait to become a "new patient" to one of these doctors after these drugs come out or you will be waiting a long time for an appointment slot (no where near 5 years though). They will absolutely prioritize their established patients first imo.

 

[all to gain]

This has been said here before and probably bears repeating: most ENTs do not do IT injections but all Otologists do. If you can't get a referral to an Otologist, find an ENT who specializes in Meniere's, they are used to doing IT injections.

Don't wait to become a "new patient" to one of these doctors after these drugs come out or you will be waiting a long time for an appointment slot (no where near 5 years though). They will absolutely prioritize their established patients first imo.

The problem is that I would almost certainly have to come to the US to get treatment so I would be a new patient. One way around this is to find an ENT/Otologist now, maybe with help of you guys in the US, to get on a patient list or to come to the US long before the drug comes out to get some type of ear exam or treatment to get on a patient list. I have no idea if any of this sounds feasible though.

 

[Jack V]

The problem is that I would almost certainly have to come to the US to get treatment so I would be a new patient. One way around this is to find an ENT/Otologist now, maybe with help of you guys in the US, to get on a patient list or to come to the US long before the drug comes out to get some type of ear exam or treatment to get on a patient list. I have no idea if any of this sounds feasible though.

There's still a lot of steps (and time) between here and there, between an ongoing phase 2 trial, a likely phase 3 trial, and whenever the drug is hopefully approved and distributed.

If I were you, I'd wait for a few more definitive signals before making phone calls.

I would imagine that following some kind of press release from Frequency Therapeutics, if it were initially available in the US, you could identify an ENT/otologist who could administer it (possibly with the help of forum members), and schedule an appointment around the time of its predicted availability.

Incidentally, if FX-322 is successful, I wouldn't be surprised if injections become an almost universally provided service of ENTs.

 

[Lucifer]

And then, knowing our luck, when everybody gets to know about it a 5-year waiting list will appear overnight to get the damn thing...

I don't think there will be a big waiting list. It depends whether the drug is covered under insurance or not. I don't think the drug will be covered under insurance straight away.

 

[Jorge1984]

How do you know your tinnitus is due to broken synapses and not hair cell loss? This has always been a grey area for me as far as knowing which one is more responsible for my hearing issues.

Someone on the Hough Ear Institute thread told me that loud music can cause the synapses to break and cause hidden hearing loss and tinnitus. I know for a fact I have synapse damage because I can hear perfectly fine but I'm guessing I have hidden hearing loss.

 

[all to gain]

There's still a lot of steps (and time) between here and there, between an ongoing phase 2 trial, a likely phase 3 trial, and whenever the drug is hopefully approved and distributed.

If I were you, I'd wait for a few more definitive signals before making phone calls.

I would imagine that following some kind of press release from Frequency Therapeutics, if it were initially available in the US, you could identify an ENT/otologist who could administer it (possibly with the help of forum members), and schedule an appointment around the time of its predicted availability.

Incidentally, if FX-322 is successful, I wouldn't be surprised if injections become an almost universally provided service of ENTs.

Yep, I am waiting. Not going to doing anything until at least the end of the year.

In the US it will become universal, no doubt, but it will take time (maybe years) for much of the rest of the world to get to that point.

 

[FGG]

Someone on the Hough Ear Institute thread told me that loud music can cause the synapses to break and cause hidden hearing loss and tinnitus. I know for a fact I have synapse damage because I can hear perfectly fine but I'm guessing I have hidden hearing loss.

FYI "hidden hearing loss" does not mean hearing loss you don't notice. It was a term coined by Charles Liberman to describe a type of hearing loss (Synaptopathy) that was "hidden" from audiologists and researchers because an audiogram does not detect it.

People with cochlear synaptopathy (aka "hidden hearing loss") often notice their hearing is very abnormal in noisy environments. I.e. they have trouble hearing the person across from them in restaurants.

Noise can damage synapses, hair cells or both. Synapses are more likely to be the most sensitive per Liberman but that was based in rodent models so no one really knows if that's universally true for people.

If you don't notice hearing loss but you have cochlear damage (e.g. from noise) it just means the damage is not widespread enough or at a high enough frequency that you don't notice. It's not diagnostic for "hidden hearing loss."

 

[Fields]

Yep, I am waiting. Not going to doing anything until at least the end of the year.

In the US it will become universal, no doubt, but it will take time (maybe years) for much of the rest of the world to get to that point.

@Diesel made a very informative post on the possible availability outside of the US, prior to becoming commercially available.

https://www.tinnitustalk.com/thread...-loss-regeneration.18889/page-267#post-521077

 

[john paul]

Can anyone summarise where we are with FX-322? Do we get Phase 2A results in October? Will they be commenting on tinnitus in the results? If 2A is success does that mean 2B will be next year 2021 and then P3, if it happens, sometime in 2022? Sorry, having a bad day, I need some light to get me through.

 

[FGG]

Can anyone summarise where we are with FX-322? Do we get Phase 2A results in October? Will they be commenting on tinnitus in the results? If 2A is success does that mean 2B will be next year 2021 and then P3, if it happens, sometime in 2022? Sorry, having a bad day, I need some light to get me through.

Tinnitus results will get reported for 2A. That much is known for sure. October was the original estimated date but who knows if they can stick to that (esp. after COVID-19).

What comes next is unknown in terms of phases. My speculation is they will probably do a Phase 2B once they figured out the dosing in Phase 2A so they can have more rigorous data to maybe skip Phase 3 with since Phase 3 doesn't have a "standard treatment" to compare with. Just my opinion, though.

 

[john paul]

Tinnitus results will get reported for 2A. That much is known for sure. October was the original estimated date but who knows if they can stick to that (esp. after COVID-19).

What comes next is unknown in terms of phases. My speculation is they will probably do a Phase 2B once they figured out the dosing in Phase 2A so they can have more rigorous data to maybe skip Phase 3 with since Phase 3 doesn't have a "standard treatment" to compare with. Just my opinion, though.

Thanks, to think that at some point in 2020 we might know for sure if we can be saved is exciting. I look foward to that day so much.

 

[WickedCarnival]

FYI "hidden hearing loss" does not mean hearing loss you don't notice. It was a term coined by Charles Liberman to describe a type of hearing loss (Synaptopathy) that was "hidden" from audiologists and researchers because an audiogram does not detect it.

People with cochlear synaptopathy (aka "hidden hearing loss") often notice their hearing is very abnormal in noisy environments. I.e. they have trouble hearing the person across from them in restaurants.

Noise can damage synapses, hair cells or both. Synapses are more likely to be the most sensitive per Liberman but that was based in rodent models so no one really knows if that's universally true for people.

If you don't notice hearing loss but you have cochlear damage (e.g. from noise) it just means the damage is not widespread enough or at a high enough frequency that you don't notice. It's not diagnostic for "hidden hearing loss."

Is there any correlation between hidden hearing loss (due to synapses damage) and loss that appears on an extended high frequency audiogram up to at least 16kHz? My thoughts initially were that they call it "hidden" because rarely any clinicians measure beyond 8kHz. It always irritated me when the professionals that I saw for tinnitus and hearing exams called my case "idiopathic" when they weren't even measuring half of the goddamn frequency range! (Newer research has shown decent reliability and not much more clinic down-time in testing higher frequencies these days so that's not a valid excuse for clinicians anymore)