Frequency Therapeutics — Hearing Loss Regeneration

[serendipity1996]

If Compassionate Use was granted for FX-322, would they still give you placebo or give you the real drug?

I think you would get the real drug.

 

[GlennS]

You get stabbed in the face for that where I grew up.

We're living in a devolving culture in the US where it's now considered acceptable call for people's heads on pikes or to be taken out and shot at dawn. It makes me weep for where we're headed as a society when everyone feels like they are literally at war with anyone they disagree with. At this rate give it a few years and the US will be very firmly in failed-state sectarian war territory with this violence-first approach.

It's not your job to be a volunteer vigilante for Frequency Therapeutics.

 

[FGG]

If Compassionate Use was granted for FX-322, would they still give you placebo or give you the real drug?

They only give you placebo for compassionate use if you stay in room 1408.

 

[Lucifer]

They only give you placebo for compassionate use if you stay in room 1408.

Haha.

 

[frpp]

They only give you placebo for compassionate use if you stay in room 1408.

For compassionate use I'll stay in room 1408, heck I'll stay room 14008 for a whole month.

 

[weab00]

For compassionate use I'll stay in room 1408, heck I'll stay room 14008 for a whole month.

There are many of us here who would chop our own limbs off just to get a chance to take these drugs.

 

[tommyd87]

Regarding delivery - This seems to be the main hurdle for Frequency Therapeutics to improve on at the moment, correct? Sure, there might be other reasons why FX-322 is working "better" in a lab setting than in humans, but surely there's a good chance that results will improve if the delivery method is improved.

I remember Carl LeBel saying something in the Tinnitus Talk Podcast about them looking heavily into different delivery methods. I haven't read or heard much about this elsewhere though. Is there any more info out there on their approach on this? What other delivery methods are they potentially exploring? Could it be anything else than injections, and/or can the type of gel and/or type of injection be improved somehow? Could this be something they can improve on in Phase 3 for example, or would they have to restart at a Phase 1?

Sorry, just blaring out questions here in hopes someone has a clue...

It is a lot easier to get redosing and reformulation done after a medicine has been approved and released because the criteria is a lot less stringent. A few techniques are also being researched now like cochlear pumping which has been shown to be very effective at getting medicine deep in the ear. Essentially if Frequency Therapeutics cannot get FX-322 working well with the lower frequencies then I certainly see them looking into a redosing with a technique like this.

The way I see things happening in relation to dosing are as follows:

1. Frequency Therapeutics tries to get FX-322 working well with multiple doses using their current chosen method of an intratympanic injection. If this works then it is a good result and Frequency Therapeutics can commence completing treatments when FX-322 is hopefully approved by the FDA. There is also the highly likely possibility Frequency Therapeutics will look at things like doing more than four injections if the multiple injection methods works like the research suggests since there will be no restrictions on how many shots they can do post approval.

2. If the dosing method of an intratympanic injection is ineffective then they will look to other methods or look at trying intratympanic injections again with a bigger volume per dosing.

3. Frequency Therapeutics won't do anything to do with redosing until after the clinical trials have been completed because they believe that they can demonstrate sufficient benefit with the current technique to pass the requirements of the FDA. Also it is inevitably much easier to deal with redosing and get approval for it once FX-322 has been approved, as a lot less requirements need to be fulfilled.

 

[d'Wooluf]

Wouldn't it be hilarious to be given a drug under 'compassionate use' and be told on your death bed that it was actually a placebo? Like 'Is this some strange use of the word compassion with which I was previously unfamiliar?' Sorry, I thought it was funny in a black kind of way. Moving right along,..

 

[Princebeyel]

If I were to participate and get the medicine, what do you think my gains would be?

 

[Gb3]

If I were to participate and get the medicine, what do you think my gains would be?

I don't think anyone can answer that question for you.

 

[Lucifer]

If I were to participate and get the medicine, what do you think my gains would be?

Hard to tell. It depends on how much cumulative damage you've got over the years. I know for a fact I have cumulative damage from listening to loud music but it doesn't show up on an audiogram.

 

[tommyd87]

Hard to tell. It depends on how much cumulative damage you've got over the years. I know for a fact I have cumulative damage from listening to loud music but it doesn't show up on an audiogram.

This. I think this is why Frequency Therapeutics is aiming to get FX-322 approved now with the four doses and is going to look at things like the benefit of more injections or new dosing methods later on when it is inevitably much simpler to do too.

The thing is though that the approval and availability of a synapse medicine is going to provide individuals with a lot of benefit since it is incredibly likely that most people have a mix of hair cell and synapse issues which won't get treated with a single medicine.

 

[FGG]

Wouldn't it be hilarious to be given a drug under 'compassionate use' and be told on your death bed that it was actually a placebo? Like 'Is this some strange use of the word compassion with which I was previously unfamiliar?' Sorry, I thought it was funny in a black kind of way. Moving right along,..

Me too. I actually laughed picturing a pinhead type figure presiding over "compassionate use." Pure dark comedy gold.

 

[FGG]

If I were to participate and get the medicine, what do you think my gains would be?

Eventually we will have that answer but the hard numbers are what these trials are trying to work out.

 

[fletchermunson]

Hi Everyone. Long time listener, first time caller. To begin, I'd just like to say that I am very grateful to everyone on this forum sharing their hopes, fears and general information. It's been a great source of relief to me over the years… optimistic and pessimistic alike.

A few lingering questions I've had:

1. Does it seem that the folks who were treated with a single dose in the first trial would have most of their hearing restored near 20 kHz and then descending in value until it reached their previously confirmed responses in the middle range? Perhaps their extended audio grams would have "U" shape?
2. Not to bring up a sore spot… but FGG mentioned that this drug caused cancer in rats when taken in large doses orally. Is there a good reason to believe it won't do the same when injected in our ears? Apologies if this has been covered.
3. My tinnitus took years to develop after confirmed hearing loss. I think it's possible that if the hearing is restored, it will take at least that long for the brain to adapt and lose the ringing. So maybe don't get worried when a recent trial participant doesn't notice a tinnitus change right away.

 

[GlennS]

Me too. I actually laughed picturing a pinhead type figure presiding over "compassionate use." Pure dark comedy gold.

 

[d'Wooluf]

Me too. I actually laughed picturing a pinhead type figure presiding over "compassionate use." Pure dark comedy gold.

Thank goodness. I was worried that I was a bit weird.

 

[Lucifer]

Anyone have an idea, after the Phase 2a clinical trial results come out, when can they get the ball rolling with starting Phase 2b/3 clinical trial for FX-322?

 

[FGG]

Thank goodness. I was worried that I was a bit weird.

It's possible we both are...

 

[Jack V]

Hi Everyone. Long time listener, first time caller. To begin, I'd just like to say that I am very grateful to everyone on this forum sharing their hopes, fears and general information. It's been a great source of relief to me over the years… optimistic and pessimistic alike.

A few lingering questions I've had:

1. Does it seem that the folks who were treated with a single dose in the first trial would have most of their hearing restored near 20 kHz and then descending in value until it reached their previously confirmed responses in the middle range? Perhaps their extended audio grams would have "U" shape?
2. Not to bring up a sore spot… but FGG mentioned that this drug caused cancer in rats when taken in large doses orally. Is there a good reason to believe it won't do the same when injected in our ears? Apologies if this has been covered.
3. My tinnitus took years to develop after confirmed hearing loss. I think it's possible that if the hearing is restored, it will take at least that long for the brain to adapt and lose the ringing. So maybe don't get worried when a recent trial participant doesn't notice a tinnitus change right away.

1. No idea.

2. No one really knows what the side effects are until the drug has been in wider circulation.

That said, you cram enough of any drug into a rat and it's going to get cancer (with the exception of New York City rats which can eat anything). I.e, I wouldn't put too much stock into that.

3. There are people who've put on hearing aids and their tinnitus immediately disappears, and it's possible yours would do the same thing with FX-322. However, again, we're reading tea leaves. Assuming it gets FDA approval, like any drug, it will likely work differently for different people.

Also, I just wouldn't put too much stock into internet hearsay at this point anyway, one way or the other.

 

[FGG]

Hi Everyone. Long time listener, first time caller. To begin, I'd just like to say that I am very grateful to everyone on this forum sharing their hopes, fears and general information. It's been a great source of relief to me over the years… optimistic and pessimistic alike.

A few lingering questions I've had:

1. Does it seem that the folks who were treated with a single dose in the first trial would have most of their hearing restored near 20 kHz and then descending in value until it reached their previously confirmed responses in the middle range? Perhaps their extended audio grams would have "U" shape?
2. Not to bring up a sore spot… but FGG mentioned that this drug caused cancer in rats when taken in large doses orally. Is there a good reason to believe it won't do the same when injected in our ears? Apologies if this has been covered.
3. My tinnitus took years to develop after confirmed hearing loss. I think it's possible that if the hearing is restored, it will take at least that long for the brain to adapt and lose the ringing. So maybe don't get worried when a recent trial participant doesn't notice a tinnitus change right away.

1. I am not sure what you mean or what you are asking. Are you saying, they got better response at 20 kHz and then less response until 8 kHz?

If so, there is no evidence of a "U shaped" response in this way.

2. In order to get the drug into the ear orally you have to give it in massive amounts. It was carcinogenic in those amounts.

Pharmacologic absorption studies were done in Phase 1. The systemic absorption/blood levels were low. Also, they found no evidence of abnormal cancerous growth when administered intratympanically.

3. It's definitely possible and even probable imo that it takes some people longer than others if it's analogous to the neuroplastic changes in mirror therapy for phantom limb (and that's an analogy more than one tinnitus researcher has used) because some people get relief faster than others in that case. I wouldn't think years, though because you are essentially doing "mirror therapy" non stop with restored hearing and not just a few times a day. A few months possibly though.

Speaking to your case though, Dr. Will Sedley said that, though hearing loss causes tinnitus, not everyone with hearing loss gets tinnitus and the reason is because of a few factors, but one is a more genetically "predictive" brain, in which less damage is needed to initiate tinnitus. You might have just crossed a necessary threshold of damage later. He also mentioned that prolonged stress seems to change your Neurochemical profile in a way that's more conducive to tinnitus generation after acoustic or other injury.

 

[Pre55ure]

A few lingering questions I've had:

1. Does it seem that the folks who were treated with a single dose in the first trial would have most of their hearing restored near 20 kHz and then descending in value until it reached their previously confirmed responses in the middle range? Perhaps their extended audio grams would have "U" shape?

I can't really answer your other questions, but I have researched this one so I'll take a stab at answering it.

This would obviously rely on what the individual's extended audiograms looked like before being treated with FX-322. If the hearing loss was the result of age - then I believe that yes a "U" shape would be most likely as high frequency hearing tends to naturally "die off" first. Noise-induced hearing loss on the other hand tends to start centered in the 4 kHz to 6 kHz range and then spread outward from there, so depending on the combination of the individual's age, noise-induced hearing damage, and (hopefully) hearing restoration, it might end up closer to a "U" but with some notches still present. Hopefully more injections or a different delivery method will eventually lead to better results across more frequencies.

 

[Philip83]

The thing is though that the approval and availability of a synapse medicine is going to provide individuals with a lot of benefit since it is incredibly likely that most people have a mix of hair cell and synapse issues which won't get treated with a single medicine.

But hasn't it been shown that FX-322 also regrows synapse connections to the hair cell once the hair cell is regrown?

Statistic rules get followed with clinical trials because this is a point of accuracy in results. Really the reality is even if something is or is not statistically significant, it does not have a bearing on whether somebody notices a gain or not. Now looking at the first FX-322 trial there tended to be some who claimed that the 10-15 dB improvement and/or the word recognition improvement is nothing fancy or significant, yet in reality those who benefited got real gains from the treatment and actually would have noticed this personally. This is why statistical analysis of certain things can be somewhat flawed and not representative of the actual benefits and improvements something can have on somebody.

Just like calling 40 dB hearing loss "mild" and only testing people's hearing up to 8 kHz and saying they have no hearing loss.

 

[serendipity1996]

But hasn't it been shown that FX-322 also regrows synapse connections to the hair cell once the hair cell is regrown?

Just like calling 40 dB hearing loss "mild" and only testing people's hearing up to 8 kHz and saying they have no hearing loss.

Yes but if you have synaptopathy without a corresponding hair cell loss, then you'll a need synapse drug too.

 

[Gb3]

Does anyone know if there is synapse damage with sudden hearing loss?

 

[FGG]

Does anyone know if there is synapse damage with sudden hearing loss?

There can be. Unfortunately, there isn't a great diagnostic test for it. A lot of people will just have to trial treat with both drugs.

 

[Loui]

I have a question regarding progenitor cells. Do we have one per hair cell or how does it work?

Unfortunately hearing loss and tinnitus runs in my family so I'll probably lose more hearing as I age. If we end up with a launch of FX-322, would it be wise to wait until I'm older if my hearing and tinnitus doesn't get worse or do we have the possibility to take it multiple times?

I can live with my tinnitus and hyperacusis for now but of course I would wish to get rid of it sooner than later

 

[Diesel]

I have a question regarding progenitor cells. Do we have one per hair cell or how does it work?

Unfortunately hearing loss and tinnitus runs in my family so I'll probably lose more hearing as I age. If we end up with a launch of FX-322, would it be wise to wait until I'm older if my hearing and tinnitus doesn't get worse or do we have the possibility to take it multiple times?

I can live with my tinnitus and hyperacusis for now but of course I would wish to get rid of it sooner than later

From what has been described by Frequency Therapeutics, there is a progenitor "support" cell for each Inner and Outer hair cell lining the cochlea. Frequency Therapeutics has described patients returning for repeat dosages; so I don't see the benefit in waiting until you get to a certain level.

 

[patorjk]

I have a question regarding progenitor cells. Do we have one per hair cell or how does it work?

You can see some nice diagrams here:

https://www.tinnitustalk.com/thread...-loss-regeneration.18889/page-328#post-539760

FX-322 acts on the Lgr5+ progenitor cells.

Unfortunately hearing loss and tinnitus runs in my family so I'll probably lose more hearing as I age. If we end up with a launch of FX-322, would it be wise to wait until I'm older if my hearing and tinnitus doesn't get worse or do we have the possibility to take it multiple times?

I can live with my tinnitus and hyperacusis for now but of course I would wish to get rid of it sooner than later

You'll be able to take it multiple times, it doesn't deplete the support cells. In fact, in one of their investor conferences they talked about the possibility of people getting a "booster" shot once a year.

 

[Jack V]

You'll be able to take it multiple times, it doesn't deplete the support cells. In fact, in one of their investor conferences they talked about the possibility of people getting a "booster" shot once a year.

Well, investors love booster shots (repeat customers)