Frequency Therapeutics — Hearing Loss Regeneration

[xCyborg]

"The clinical evaluation of FX-322 for hearing restoration is a priority for us based on the unmet medical need of millions of patients around the world who have lost varying degrees of hearing function from chronic noise exposure or sudden hearing loss, and we look forward to reporting the results from this study toward the end of 2018."

The question is will they report on the efficacy of the drug, which is neither the primary nor secondary outcome measure.

And will this internal data (which most likely will collect) influence the timeline of the phase 2 trial?

 

[d'Wooluf]

The question is will they report on the efficacy of the drug, which is neither the primary nor secondary outcome measure.

I'd say they will if it suits them. What exactly suits them I'm not sure.

And will this internal data (which most likely will collect) influence the timeline of the phase 2 trial?

No difference: Why do a phase 2 trial at all?
Clear positive difference: Why wait?
Marginal or unclear: Back to the drawing board for a while and do some serious thinking I guess. If there were improvement in some subjects and not others, they might spend resources in exploring the reasons why before the next trial.

Would the fda accept that internal data as relevant when it comes to approving the next study? If all the safety endpoints were achieved, could they jump straight to Phase 3? Many questions.

 

[Flamingo1]

placebo? wtf? If your hearing improves, it can be determined using an audiogram. You can't mentally make it better. Why waste someone's time and hope on a placebo, especially when you are having a needle go through your eardrum?

The information page says they are only looking at the safety of FX-322 in this trial.

 

[IvanRus]

@Aaron123 @d'Wooluf @Tempest @Silvio Sabo @Markku

Honestly, with all the desire to do so, it is difficult for me to imagine such an event - the company suddenly having learned to regenerate (re-grow) the auditory hair cells.

It is difficult to imagine, guided by the following laws of logic:

- If Frequency is close to that (even in 7-10-15 years from the implementation), in order to regenerate the inner ear, then why do other companies do the same? For example, Decibel Therapeutics, Regain? Would it be justifiable for them, from a financial point of view, to conduct the same kind of research if they knew for sure that a regeneration technology was about to appear on the market?

- I also studied the activities of Stanford University, and they say that in the coming years they will focus on studying genes that affect hearing damage. Why would they do this if a drug could appear on the market that regenerates the hearing?

- Besides, feeling that the revolutionary technology of repairing auditory hair cells should appear on the market, manufacturers of Hearing Aids and implants should have seriously strained and poured into their lobbyists huge funds to prevent this. You imagine that the market for hearing aids is a multi-billion dollar market. And what, can you imagine that in 10-15 years it should collapse because of the revolutionary technologies of regeneration?

I really want Frequency and other companies engaged in regeneration, to successfully enter the market and give us this miracle.

Perhaps, at first everything will not be so smooth - maybe the medicine will work only with recent damage, or a certain type of damage.

I never received an answer from them, whether they expect to treat all people, or only those with an acoustic trauma.

What do you think about it?

 

[streeter1985]

If Frequency is close to that ....

Well I am not into law or the rules for clinical trials between many companies at the same time but I think its a free market....I could think that the idea overall looks promising and scientists know that so its a run to the results (see phase 1.5 from frequency - phase 1.5?? I think they want answers faster) ...its an idea....like any new technical product....first company who can proof it will have a good income based on a patent for years - connected to the drug and the process.

I also studied the activities...

because frequency therapeutics only focus on "mild" hearing loss. this is just a "small" part of the problem. If you think about hidden hearing loss maybe you have a complete loss at one frequency that you cant measure. From the theory a complete loss cant be cured by Frequency Therapeutics so their is still need for a gene therapy - or just think about deaf people.

Besides, feeling that the revolutionary technology of repairing auditory

There are many thoughts about that. Let me give you a different view. Think about people with hearing aids or implants and what insurances have to pay a life-time and not even only the devices also the therapists, psychological help and many other treatments that have zero cure, people who cant work anymore etc etc. I am pretty sure the insurances WANT a cure that really helps people so that they can stop with that life-time support stuff. I think that cure is so important for mankind that no lobbyist can stop it from the market. It doesnt stop from rich nor poor people.

It sounds strange but in the end maybe the insurances have to pay less with such a cure? Thats my view on the situation. I am just afraid that they have to pay a lot in the beginning

I never received an answer

The trial focus on acoustic trauma and the answer on that one seems easy to me. The acoustic trauma is something you can create with animals in a lab very easily so I think most approaches will focus on acoustic traumas at first.

 

[Rubenslash]

@Aaron123 @d'Wooluf @Tempest @Silvio Sabo @Markku



I never received an answer from them, whether they expect to treat all people, or only those with an acoustic trauma.

What do you think about it?

Has been mentioned several times by Frequency that not only people with acoustric trauma are included, but also people with SSHL due to other causes...Has even been discussed in the previous page.

 

[JohnAdams]

I'm a little on the fence about changing my genes. That could have some horrible side effects

What if you turned into Gene Simmons?

 

[JohnAdams]

The question is will they report on the efficacy of the drug, which is neither the primary nor secondary outcome measure.

And will this internal data (which most likely will collect) influence the timeline of the phase 2 trial?

I think they're playing it by ear.
*drops the mic*

 

[d'Wooluf]

Honestly, with all the desire to do so, it is difficult for me to imagine such an event - the company suddenly having learned to regenerate (re-grow) the auditory hair cells.

I think FX are possibly the best self-promoters of all of the labs working in the field. Robert Langer, one of their co-founders is as famous for his entrepeneurship as he is for is science. But look at their records, the institutions they come from, and you'll see that they are top-bracket scientists.

Other labs will keep doing what they do, because at this point in time the field is wide open. Even if FX-322 is a success, there's no reason why another lab can't develop something better, or help fill in the gaps. It's unlikely (or so I've read) that there is a universal solution to hearing loss.

I think you're right to be a little skeptical, but what I see are some very smart people in labs all of the world who now see in which direction the solution lies. So, although I'm more cautious than many people here, I also believe that progress is inevitable. The timing is in dispute however.

Here are five outfits who seem to be working on similar approaches. I'm sure there are more.

1. Frequency Therapeutics
2. Audion/ReGain Hearing Project
3. James Hudspeth/Rockefeller Uni https://www.scientificamerican.com/article/theres-an-inverse-piano-in-your-head/
4. Acousia http://www.acousia.com/
5. Hough Ear Institute http://houghear.org/

 

[Flamingo1]

I'm a little on the fence about changing my genes. That could have some horrible side effects

What if you turned into Gene Simmons?

Case in point.

 

[JohnAdams]

I think FX are possibly the best self-promoters of all of the labs working in the field. Robert Langer, one of their co-founders is as famous for his entrepeneurship as he is for is science. But look at their records, the institutions they come from, and you'll see that they are top-bracket scientists.

Other labs will keep doing what they do, because at this point in time the field is wide open. Even if FX-322 is a success, there's no reason why another lab can't develop something better, or help fill in the gaps. It's unlikely (or so I've read) that there is a universal solution to hearing loss.

I think you're right to be a little skeptical, but what I see are some very smart people in labs all of the world who now see in which direction the solution lies. So, although I'm more cautious than many people here, I also believe that progress is inevitable. The timing is in dispute however.

Here are five outfits who seem to be working on similar approaches. I'm sure there are more.

1. Frequency Therapeutics
2. Audion/ReGain Hearing Project
3. James Hudspeth/Rockefeller Uni https://www.scientificamerican.com/article/theres-an-inverse-piano-in-your-head/
4. Acousia http://www.acousia.com/
5. Hough Ear Institute http://houghear.org/

Damn I sure picked the right time to get tinnitus. I just want my life back. This shit sucks.

 

[JohnAdams]

Hair Cell Regeneration Trials

1. USA: Frequency Therapeutics (drug: FX-322)
   • https://www.alamoent.com/wp-content/uploads/2018/07/Hearing-Loss-Study.pdfvvv
   • https://clinicaltrials.gov/ct2/show/NCT03616223?term=FX-322&rank=1
2. UK: Audion - Regain Trial
   • https://www.regainyourhearing.eu/trial/
3. USA: Novartis
   • http://www.trials.novartis.com/en/clinical-trials/hearing-restoration-clinical-trial/
   • http://www.trials.novartis.com/en/c...storation-clinical-trial/information/contact/

Other

1. Sensorion (drug: SENS-401 for Sudden SensoriNeural Hearing Loss (SSNHL))
   1. A phase 2 study is planned for 2018.
2. Otonomy is planning trials for 2019

But I don't know which of them are still look for participants!

With so much activity going on it would seem like a good bet that we will have answer about tinnitus relatively soon.

 

[JohnAdams]

Hair Cell Regeneration Trials

1. USA: Frequency Therapeutics (drug: FX-322)
   • https://www.alamoent.com/wp-content/uploads/2018/07/Hearing-Loss-Study.pdfvvv
   • https://clinicaltrials.gov/ct2/show/NCT03616223?term=FX-322&rank=1
2. UK: Audion - Regain Trial
   • https://www.regainyourhearing.eu/trial/
3. USA: Novartis
   • http://www.trials.novartis.com/en/clinical-trials/hearing-restoration-clinical-trial/
   • http://www.trials.novartis.com/en/c...storation-clinical-trial/information/contact/

Other

1. Sensorion (drug: SENS-401 for Sudden SensoriNeural Hearing Loss (SSNHL))
   1. A phase 2 study is planned for 2018.
2. Otonomy is planning trials for 2019

But I don't know which of them are still look for participants!

From the Audion trial page "if you also suffer from tinnitus, and this is more of a problem to you than your hearing loss, you will not be eligible to take part."

*farts*
WHY?

 

[JohnAdams]

Okay, I emailed Audion and asked why they are excluding tinnitus sufferers. They got back to me in like 20 minutes.

Here's the attachment:

 

[Gorbeh3]

I don't understand the whole "we aren't testing for efficacy". The people being tested aren't having cochlear implant surgery, so even if they don't specifically test the subjects after with an audiogram, won't the subjects know regardless? They could even go to their own independent audiologist and get tested to see the exact results.

 

[TheDanishGirl]

From the Audion trial page "if you also suffer from tinnitus, and this is more of a problem to you than your hearing loss, you will not be eligible to take part."

*farts*
WHY?

Because this drug is for hearing loss and not tinnitus. Their priority is not curing tinnitus but hearing loss.

 

[Clmnt]

http://www.frequencytx.com/news-events/news-events-press-release-08-7-2018.php

 

[d'Wooluf]

I don't understand the whole "we aren't testing for efficacy". The people being tested aren't having cochlear implant surgery, so even if they don't specifically test the subjects after with an audiogram, won't the subjects know regardless? They could even go to their own independent audiologist and get tested to see the exact results.

They'll have to test their subjects' hearing. If nothing else, they'll have to check that the treatment doesn't make it worse. What they'll do with the information is what we've been wondering.

 

[d'Wooluf]

Here's the attachment:

That's kind of interesting. Actually really comprehensive and 'professional'. They seem to be taking patient safety very seriously. Much more seriously than FX from the little we know.

 

[xCyborg]

They'll have to test their subjects' hearing. If nothing else, they'll have to check that the treatment doesn't make it worse. What they'll do with the information is what we've been wondering.

Dude just imagine if does make it worse but treat tinnitus

 

[JohnAdams]

Dude just imagine if does make it worse but treat tinnitus

closer to silence my friend...…..

 

[IvanRus]

Has been mentioned several times by Frequency that not only people with acoustric trauma are included, but also people with SSHL due to other causes...Has even been discussed in the previous page.

All the same, apparently now they are focused only on the noise induced by hearing loss. This is stated on the official website:

"Frequency is developing progenitor cell activation (PCA™) therapies, innovative disease-modifying products that temporarily activate cellular regeneration at specific sites in the body for unprecedented healing benefits. Frequency's initial focus is on chronic noise induced hearing loss."
http://www.frequencytx.com/our-approach/hearing-and-beyond.php

Although I really do not understand the fundamental difference - still in most cases it is the death of hair cells.

 

[Silvio Sabo]

@Aaron123 @d'Wooluf @Tempest @Silvio Sabo @Markku

Honestly, with all the desire to do so, it is difficult for me to imagine such an event - the company suddenly having learned to regenerate (re-grow) the auditory hair cells.

It is difficult to imagine, guided by the following laws of logic:

- If Frequency is close to that (even in 7-10-15 years from the implementation), in order to regenerate the inner ear, then why do other companies do the same? For example, Decibel Therapeutics, Regain? Would it be justifiable for them, from a financial point of view, to conduct the same kind of research if they knew for sure that a regeneration technology was about to appear on the market?

- I also studied the activities of Stanford University, and they say that in the coming years they will focus on studying genes that affect hearing damage. Why would they do this if a drug could appear on the market that regenerates the hearing?

- Besides, feeling that the revolutionary technology of repairing auditory hair cells should appear on the market, manufacturers of Hearing Aids and implants should have seriously strained and poured into their lobbyists huge funds to prevent this. You imagine that the market for hearing aids is a multi-billion dollar market. And what, can you imagine that in 10-15 years it should collapse because of the revolutionary technologies of regeneration?

I really want Frequency and other companies engaged in regeneration, to successfully enter the market and give us this miracle.

Perhaps, at first everything will not be so smooth - maybe the medicine will work only with recent damage, or a certain type of damage.

I never received an answer from them, whether they expect to treat all people, or only those with an acoustic trauma.

What do you think about it?

Just answer the following questions and you will see why others are continuing their research: How many different types of pain medication are there? Why don't we have just THE ONE?

 

[CricketEars]

Just answer the following questions and you will see why others are continuing their research: How many different types of pain medication are there? Why don't we have just THE ONE?

Exactly! Different methods of action

 

[d'Wooluf]

"Frequency is developing progenitor cell activation (PCA™) therapies, innovative disease-modifying products that temporarily activate cellular regeneration at specific sites in the body for unprecedented healing benefits. Frequency's initial focus is on chronic noise induced hearing loss."
http://www.frequencytx.com/our-approach/hearing-and-beyond.php

Although I really do not understand the fundamental difference - still in most cases it is the death of hair cells.

It makes sense to focus on something where the cause is 1) known 2)simple 3)common and 4)won't come back to bite you (as long as you don't put yourself in that danger again). Hearing loss with a genetic component introduces a whole lot of questions.

 

[d'Wooluf]

Just answer the following questions and you will see why others are continuing their research: How many different types of pain medication are there? Why don't we have just THE ONE?

Well, we don't even have "THE ONE" in hearing loss treatment right now. We have a lot of hopes, that's all. So, keep going with the research people.

 

[Contrast]

Well, we don't even have "THE ONE" in hearing loss treatment right now. We have a lot of hopes, that's all. So, keep going with the research people.

no one knows if a huge bio complication gets in the way and it could pretty much all go wrong

Hypothetical example of what if's:

1:What if hair cells grow back but with very little synaptic ribbons so the hearing is pretty much mumbled garabage?

2:"What if FX-322 has trouble navigating the cochlea, (the drug works) but it's gel cannot travel the cochlea

3: What if tinnitus ends up centralizing in regions of the brain that are totally unrelated to hearing and even if the original damage is corrected the tinnitus consist?

4: What if the drug barely works, or if it has harmful side effects?

This is all total speculation, but I have good reasons not to be overly optimistic.

 

[d'Wooluf]

This is all total speculation, but I have good reasons not to be overly optimistic.

You have every reason to be optimistic, but also every reason to be realistic. One doesn't cancel out the other. I see people pretty much mentally banking their entire futures on the outcome of this one trial. It's just not healthy in my opinion.

This sub-topic started with someone suggesting that other researchers had not given up their research in the face of what Frequency Therapeutics is doing therefore what Frequency Therapeutics is doing is not valid. That's turning a positive into a negative. The positive is that there are many very smart people moving towards various solutions. If it's not FX it will probably be someone else.

But really, obsessing over *any* possible solution is not a good thing. I think we should concentrate on living our lives (including mindfulness, yoga, healthy eating, and all those other useless things) as best we can, but with a healthy measure of optimism that treatment might come in our lifetimes. The first humans in history who can say that.

 

[JohnAdams]

Tell me please, the mechanism of regeneration of the inner ear (even theoretically) developed by the companies Frequency Therapeutics and Decibel Therapeutics is aimed only at the regeneration of the outer hair cells? Or does it include the regeneration of inner hair cells?

Will it help people with damage to the inner hair cells?

I just cannot find the information which cell division affects aminoglycosides (gentamicin) with ototoxicity, only the outer hair cells?

Who knows about this? Huge thanks in advance!

Look up ly411575 cochlea

 

[Silvio Sabo]

Well, we don't even have "THE ONE" in hearing loss treatment right now. We have a lot of hopes, that's all. So, keep going with the research people.

Sure. But the same situation was once upon a time in pain medication as well. Until the first one came. They actually still actively research for new and better ones. So just because a drug or a treatment for something hits the market the research typically doesn't stop. We will have the first one at one point in time and then a second, and a third and so on and so on.