Frequency Therapeutics — Hearing Loss Regeneration

[weab00]

I would further speculate that they mean 4 kHz, 6 kHz, and 8 kHz band improvements; because "bands" are typically used in reference to the standard audiogram.

It would be cool if this were true, since it'd mean Frequency Therapeutics has improved their dosing method to reach lower frequencies.

 

[scotty03874]

I'm just going to leave this here

View attachment 41940

Darren, can you message this person again and please get more details? Dosages, dB improvements and at what frequencies?

 

[FGG]

What about their tinnitus?

Wherever you found that, can you ask the person please?

If they ask, can they tone match their tinnitus? Because if they have tinnitus at 8 kHz and improvements at 8 kHz, they should see improvements but if their worst tinnitus is at say at 1000 Hz, maybe not.

 

[Diesel]

If they ask, can they tone match their tinnitus? Because if they have tinnitus at 8 kHz and improvements at 8 kHz, they should see improvements but if their worst tinnitus is at say at 1000 Hz, maybe not.

Are we even sure this person has tinnitus? Some with measurable hearing loss on the standard audiogram do not.

I feel like an improvement would be the first thing someone would mention if they did have tinnitus. But, maybe I'm just too close to the issue.

 

[Jack V]

False and misleading statements or claims could be made about the benefit of FX-322 from the illegitimate and unverified claims.

Those won't compromise the results of the trial.

The value of the trial, as frustrated as we may be by its length, is that it's based on data, not statements.

 

[Jack V]

This is one of the more interesting aspects of this trial to me. I really hope the four shots makes a difference compared to two. If that is indeed the case, the treatment could probably be extended for some (once released) to give maximum benefit.

Depending on age, genetics and amount of hearing loss, some people might just need 1-2 shots, while others might need 5-10.

Agreed.

Furthermore, assuming it gets FDA approval, ENTs have off-label flexibility, including for additional shots.

In other words, the trial might determine that for 90% of the people, there could be a benefit to a 2nd shot but no more, and the FDA approves a 2-dose protocol.

That wouldn't necessarily stop your ENT from prescribing additional shots if they think the potential benefit is worth the risk.

 

[Philip83]

That wouldn't necessarily stop your ENT from prescribing additional shots if they think the potential benefit is worth the risk.

At this point, do we actually know of any risks with the compound itself?

Complications with a badly performed injection and/or damaged eardrum is one I guess.

 

[Philip83]

Are we even sure this person has tinnitus? Some with measurable hearing loss on the standard audiogram do not.

I feel like an improvement would be the first thing someone would mention if they did have tinnitus. But, maybe I'm just too close to the issue.

Yeah, my thought too. My mom had no tinnitus with a hearing loss down to like 70-80 dB. Once she started going lower however, her tinnitus started.

 

[patorjk]

Are we even sure this person has tinnitus? Some with measurable hearing loss on the standard audiogram do not.

I feel like an improvement would be the first thing someone would mention if they did have tinnitus. But, maybe I'm just too close to the issue.

Yes, they have tinnitus. I know where that poster's post came from and they have previously talked about their tinnitus (though they have not stated if their tinnitus has improved). I haven't talked to them about the trial because it seemed ethically weird to do so.

 

[weab00]

At this point, do we actually know of any risks with the compound itself?

Complications with a badly performed injection and/or damaged eardrum is one I guess.

Didn't they find it caused cancer in rats at high enough intratympanic doses or was that another drug? The side effects seem minimal thus far.

 

[Diesel]

Yeah, my thought too. My mom had no tinnitus with a hearing loss down to like 70-80 dB. Once she started going lower however, her tinnitus started.

This is interesting. I have continued to speculate that for those with NIHL that starts with high-frequency hearing loss, that there is a correlation between the high-frequency hearing loss and tinnitus. If FX-322 treats tinnitus for those that experience it, it would be really interesting for Frequency Therapeutics to show how the improved high-frequency audiogram led to a reduction in tinnitus.

We would then know potentially that say, high-frequency losses at 70 dB+ causes tinnitus in NIHL cases, and getting it to regenerate to say 20 dB starts to have a positive impact... this would really help treat the condition.

 

[frpp]

Didn't they find it caused cancer in rats at high enough intratympanic doses or was that another drug? The side effects seem minimal thus far.

No. Allegedly that was through ingestion. Perfectly safe so far in the ear.

 

[paul mclean]

Good to hear some positive anecdotal evidence but this just makes me more keen for March and May 2021.

We still don't know the doses they are using and it's still only in one ear. The other ear being used as a control.

If people are experiencing such a positive response from 1-4 shots of FX-322 in one ear, this is really exciting news.

In Phase 3 they could up the dose even further once they have more of a grasp on its safety and efficacy.

Receiving 4 shots of FX-322 in both my ears is definitely one of my most desired things I want to happen in my life right now!

 

[GBB]

This is interesting. I have continued to speculate that for those with NIHL that starts with high-frequency hearing loss, that there is a correlation between the high-frequency hearing loss and tinnitus. If FX-322 treats tinnitus for those that experience it, it would be really interesting for Frequency Therapeutics to show how the improved high-frequency audiogram led to a reduction in tinnitus.

We would then know potentially that say, high-frequency losses at 70 dB+ causes tinnitus in NIHL cases, and getting it to regenerate to say 20 dB starts to have a positive impact... this would really help treat the condition.

I have pretty bad tinnitus and on a standard audiogram 15 dB is my highest loss (though haven't checked above 8 kHz). I hope it is the case that for each of us, some level of lost input is enough to trigger tinnitus, and that restoring input fixes the issue.

 

[Chriscom]

I honestly don't care if they broke their NDA if it's an accurate and truthful account. They are not going to placebo their fellow participants into hearing better by broadcasting positive news.....

Actually, they could, that's part of how the placebo effect works. And the online hearing-challenged and tinnitus community is small and connected enough for this to spread like wildfire. And there's no way to determine if this is accurate and truthful.

Of course we're human beings and many who are suffering from this are encouraged by this anecdote, especially those who suffer worse than I do (which is plenty bad enough). I'd like to see the needle threaded between scraps of info here and there to keep folks' heads above water, but not enough to damage the research and further postpone effective treatment.

 

[Gb3]

Yes, they have tinnitus. I know where that poster's post came from and they have previously talked about their tinnitus (though they have not stated if their tinnitus has improved). I haven't talked to them about the trial because it seemed ethically weird to do so.

Same here.

 

[L34]

This is interesting. I have continued to speculate that for those with NIHL that starts with high-frequency hearing loss, that there is a correlation between the high-frequency hearing loss and tinnitus. If FX-322 treats tinnitus for those that experience it, it would be really interesting for Frequency Therapeutics to show how the improved high-frequency audiogram led to a reduction in tinnitus.

We would then know potentially that say, high-frequency losses at 70 dB+ causes tinnitus in NIHL cases, and getting it to regenerate to say 20 dB starts to have a positive impact... this would really help treat the condition.

I don't know if you can use this info, but I have NIHL and tinnitus. My audiogram shows a loss of 30 dB at 6000 Hz in one ear. That is the tinnitus ear... other frequencies are just 5-10 dB (so basically fine I guess).

 

[GBB]

Actually, they could, that's part of how the placebo effect works. And the online hearing-challenged and tinnitus community is small and connected enough for this to spread like wildfire. And there's no way to determine if this is accurate and truthful.

Of course we're human beings and many who are suffering from this are encouraged by this anecdote, especially those who suffer worse than I do (which is plenty bad enough). I'd like to see the needle threaded between scraps of info here and there to keep folks' heads above water, but not enough to damage the research and further postpone effective treatment.

Explain to me how you can placebo better hearing.

 

[tommyd87]

Explain to me how you can placebo better hearing.

I believe that the placebo effect was ruled out very early on by the work. Weren't we told that you either hear or you don't hear and you can't do anything really to help you hear better like you can to make you see better such as squinting your eyes by Carl LeBel?

 

[Chriscom]

Explain to me how you can placebo better hearing.

If you would like to learn more about placebo effects and hearing, googling up some studies isn't difficult. Especially in relation to hearing aid trials. Here's one:

Placebo effects in hearing-aid trials are reliable

"Participants compared two devices that were acoustically identical, except one was described as "new" and the other as "conventional". Participants completed a speech-in-noise test, sound quality ratings, and rated overall personal preference for both hearing aids.

"Conclusion: Placebo effects reliably impact on hearing-aid trials. In order to control for placebo effects, double-blind methodology is optimal. However, when double-blinding is not possible other strategies may be appropriate."

 

[tommyd87]

Agreed.

Furthermore, assuming it gets FDA approval, ENTs have off-label flexibility, including for additional shots.

In other words, the trial might determine that for 90% of the people, there could be a benefit to a 2nd shot but no more, and the FDA approves a 2-dose protocol.

That wouldn't necessarily stop your ENT from prescribing additional shots if they think the potential benefit is worth the risk.

I wouldn't be surprised if Frequency Therapeutics took FX-322, showed that it provides pretty positive benefits with multi dosing and as a result used this data to prove to the FDA that it works so they could seek approval for its use.

Then after FX-322 is approved, factors like further dosing such as getting 8 shots and also redosing to get it releasing deeper in ear will be looked at. This way Frequency Therapeutics won't have to hold up the trial's progression by delaying it further due to the time taken to undertake further doses or by having to revisit all aspects of the trial process due to a new formulation.

Much simpler to get FX-322 approved and make these changes after, particularly when there is nothing stopping ENTs from issuing more than four doses off-label once it is approved.

 

[tommyd87]

If you would like to learn more about placebo effects and hearing, googling up some studies isn't difficult. Especially in relation to hearing aid trials. Here's one:

Placebo effects in hearing-aid trials are reliable

"Participants compared two devices that were acoustically identical, except one was described as "new" and the other as "conventional". Participants completed a speech-in-noise test, sound quality ratings, and rated overall personal preference for both hearing aids.

"Conclusion: Placebo effects reliably impact on hearing-aid trials. In order to control for placebo effects, double-blind methodology is optimal. However, when double-blinding is not possible other strategies may be appropriate."

This study is saying do what Frequency Therapeutics is doing. Do a double blinded clinical trial.

There is also a massively significant difference between what a hearing aid actually does and what a medicine like FX-322 does though. Therefore the argument I'd make is that this tends to not be comparable. Consequently unless we see any different outcomes in Phase 2 whereby people benefit from the placebo, I think that there tends to be a pretty good set of data from Phase 1 that shows only those who got the medicine actually benefitted.

 

[Diesel]

If you would like to learn more about placebo effects and hearing, googling up some studies isn't difficult. Especially in relation to hearing aid trials. Here's one:

Placebo effects in hearing-aid trials are reliable

"Participants compared two devices that were acoustically identical, except one was described as "new" and the other as "conventional". Participants completed a speech-in-noise test, sound quality ratings, and rated overall personal preference for both hearing aids.

"Conclusion: Placebo effects reliably impact on hearing-aid trials. In order to control for placebo effects, double-blind methodology is optimal. However, when double-blinding is not possible other strategies may be appropriate."

Ahh I see we're back to the old "Must be a placebo effect" conversation topic... I'll let someone else take this one... I'm sure it'll come up the day after the Phase 2A results are posted too...

You quoted the recommendation used in the FX-322 trial to reduce the placebo effect: Blinding. FX-322 is a Quadruple-blinded trial. This reduces variability caused by the placebo effect.

 

[serendipity1996]

Actually, they could, that's part of how the placebo effect works. And the online hearing-challenged and tinnitus community is small and connected enough for this to spread like wildfire. And there's no way to determine if this is accurate and truthful.

Of course we're human beings and many who are suffering from this are encouraged by this anecdote, especially those who suffer worse than I do (which is plenty bad enough). I'd like to see the needle threaded between scraps of info here and there to keep folks' heads above water, but not enough to damage the research and further postpone effective treatment.

Yes, I have already seen this posted elsewhere. I don't want to be a 'killjoy' but my worry is that this patient has technically broken their NDA and this could have an impact on the trial. Maybe I'm just being paranoid but what if they halted the trial because of this?

 

[Chriscom]

I believe that the placebo effect was ruled out very early on by the work. Weren't we told that you either hear or you don't hear and you can't do anything really to help you hear better like you can to make you see better such as squinting your eyes by Carl LeBel?

To be clear, I am not saying that the preliminary, promising results of this drug were the result of a placebo effect, or that this particular NDA-breaking participant (if it's for real) is just experiencing a placebo effect. I'm saying the placebo effect is possible, and that's one reason reputable companies use double-blinded trials--and have people sign NDAs.

 

[Philip83]

This is interesting. I have continued to speculate that for those with NIHL that starts with high-frequency hearing loss, that there is a correlation between the high-frequency hearing loss and tinnitus. If FX-322 treats tinnitus for those that experience it, it would be really interesting for Frequency Therapeutics to show how the improved high-frequency audiogram led to a reduction in tinnitus.

We would then know potentially that say, high-frequency losses at 70 dB+ causes tinnitus in NIHL cases, and getting it to regenerate to say 20 dB starts to have a positive impact... this would really help treat the condition.

I think it's reasonable to assume that tinnitus usually appears after a more severe NIHL, like a noise trauma/shock. A slow "normal" wear and tear on your ears throughout life does not seem to trigger tinnitus as easily (as most people do suffer hearing loss throughout life, but only a few develop tinnitus). But when you get into the severe hearing loss regions of say 70+ dB, maybe there's just so much damage that tinnitus starts to rear its head no matter what.

 

[Chriscom]

Ahh I see we're back to the old "Must be a placebo effect" conversation topic... I'll let someone else take this one... I'm sure it'll come up the day after the Phase 2A results are posted too...

You quoted the recommendation used in the FX-322 trial to reduce the placebo effect: Blinding. FX-322 is a Quadruple-blinded trial. This reduces variability caused by the placebo effect.

Will you let someone else focus on what I said, and not what you imagined I said?

The distinctions I'm drawing are not complicated.

 

[Ozwel]

I have pretty bad tinnitus and on a standard audiogram 15 dB is my highest loss (though haven't checked above 8 kHz). I hope it is the case that for each of us, some level of lost input is enough to trigger tinnitus, and that restoring input fixes the issue.

No one knows. Many people around here tend to think so though (with no scientific evidence).

 

[Lucifer]

Ahh I see we're back to the old "Must be a placebo effect" conversation topic... I'll let someone else take this one... I'm sure it'll come up the day after the Phase 2A results are posted too...

You quoted the recommendation used in the FX-322 trial to reduce the placebo effect: Blinding. FX-322 is a Quadruple-blinded trial. This reduces variability caused by the placebo effect.

There is no way that it's a placebo. The only way I could see this fucking up is the audiologists purposely increasing the volume to make it look like the participants had improved hearing, but the likelihood of that is low, they would not want the company to get a bad reputation.

 

[tommyd87]

Ahh I see we're back to the old "Must be a placebo effect" conversation topic... I'll let someone else take this one... I'm sure it'll come up the day after the Phase 2A results are posted too...

You quoted the recommendation used in the FX-322 trial to reduce the placebo effect: Blinding. FX-322 is a Quadruple-blinded trial. This reduces variability caused by the placebo effect.

This also happened after the Phase 1/2 results and again in that article. It's actually interesting that there were no comments about the placebo effect after the 21 months assessment. I wonder whether some claiming placebo promptly decided to stay mum.