Frequency Therapeutics — Hearing Loss Regeneration

Tinnitus usually being an outcome/symptom of hearing loss is the view that I also share. It seems quite obvious that FX-322 helps with hair cell restoration. Right now it looks like synapses might also get treated by FX-322. The question is we don't know how much synapses will benefit from FX-322 at this time.

Therefore I think that if you need FX-322 for hearing loss, then it is easy to prove that you are obtaining it for its primary purpose and at the moment it is relatively clear that FX-322 has demonstrated benefit for this. Furthermore, there is a strong case to be made that if you are using FX-322 for hair cell regrowth then this should be a valid reason to get insurers to add this treatment to their list of covered treatments.

However, FX-322's benefit on synapses is not yet proven and is simply anecdotal. Proof won't be obtained until the testing outcomes are received from the current clinical trial. The fact that the synapses are being looked at as a secondary outcome indicates that this treatment need could be refused and/or deliberately overlooked by insurers.

Subsequently I would also note that it may be entirely possible that insurers refuse to cover FX-322 and associated treatments entirely on the basis that they use the same sort of ruling as they do with the hearing aids now and/or they simply just decide not to actually cover it.

I still think that a top priority for Frequency Therapeutics is to get this treatment covered. Consequently it would not be surprising seeing Frequency Therapeutics take this back through the trial phases once more to cover it for other indications like synapse growth should it be deemed that this turns out to be necessary to get FX-322 covered for all possible indications that it can be used for. This way Frequency Therapeutics won't be delaying people from obtaining FX-322 who either can get it initially for hearing loss or obviously those who would pay for out-of-pocket off-label. Frequency Therapeutics would then be doing the right thing by their customers and also their stakeholders since ultimately this should mean that there is a bigger uptake and bigger sales because more people will be able to get it as they won't need to fork out cash to pay for FX-322.

 

It might be a phase 2b since they actually don't need to do a phase 3 before they can release FX-322. It is dependent on whether we will see Frequency Therapeutics grant compassionate access and allow people to obtain it after phase 2a. It is evident from the reports and Frequency Therapeutics' comments that there is a reasonable possibility that the next trial could be their final (known as a pivotal) phase.

 

How do you get this covered if you have noise-induced tinnitus and no hearing loss on an audiogram? I guess you could just intentionally fail the audiogram?

 

I've got slight hearing loss on a standard audiogram (starts dipping at 6 kHz to -25 dB at 8 kHz). I will get an extended audiogram at some point and expect it to show a lot more.

I wonder if 8 kHz - 20 kHz hearing loss would qualify as hearing loss to an insurer?

 

It would qualify as hearing loss to an insurer; and I would argue that Frequency Therapeutics has already proven that.

They’ve done so in the Phase 1/2 by showing that improving the high frequency results in significant improvement in word score.

 

It isn’t I think going to matter so much as to what we would think an insurer might cover as a hearing loss but rather it would be probably what would an insurer get away with not covering. Because I can see many insurers trying to not cover these super expensive treatments if they don’t have to.

 

Basically I could be off the planet with this thought, but I reckon that the best thing to do would be to wait for one of the synapse treatments that are being researched. I reckon that if these treatments help tinnitus then there wouldn’t be much of an issue actually getting these covered if they are available through insurance. I think that there is a fair chance you may have synapse damage and as a result reading the research details, I think that this might cause some tinnitus too.

 

Unless they'd pay more for other services like counseling.

 

That's the thing isn't it. You could see them trying to avoid it with some kind of technicality that high frequency hearing loss isn't what you'd class as 'everyday hearing'. Although we know it is very important as per @Diesel reply above, sufferers could have a fight on their hands for a while. Hope not though, just a what if.

 

Frequency Therapeutics as we all know is a Bio-Tech research company based in the United States and they are well aware of how the health insurance industry in the U.S. can be quite selective as to what they cover and what they will not cover. I must differ with you in regard with this being a top priority for Frequency Therapeutics as well as the notion of this company returning through the trial phases in order to have anything in their pipeline covered by insurance for the mere fact of making it more widely available to the populace.

Pharmaceutical and Bio-Tech companies do not involve themselves in what a insurance company will or will not cover. When FX-322 becomes available, at the delight of hearing loss and tinnitus patients and stockholders, it is for the insurance companies to decide what to cover since the ball is now in their court. It would be in their best interest to consider coverage especially if the words-in-noise scores are significantly improved. These scores are a huge factor and will be considered a breakthrough in that hearing aids are not capable of providing this unmet need.

I have no idea how this would work in Australia, Canada, and Great Britain as these countries and others would be dealing with Astellas. However, in the United States, Frequency Therapeutics could basically care less what health insurers choose to do.

 

Perhaps the progression of hair cell regeneration by FX-322 from the outer edge of the cochlea to the inside may be similar to the action of the two proteins in the next article.
Not just due to the physical structure of the cochlea ...
Doesn't this mean that FX-322 has a natural reproduction?

https://www.hopkinsmedicine.org/new...tore-damaged-sound-detecting-cells-in-the-ear

 

If that’s the reality then it makes a lot more sense. I agree that logically Frequency Therapeutics would want to just get the treatment released. However then I look at other organisations like Hough Ear Institute which claim that they need to get the treatment through the trials for various indications in order to obtain insurance coverage. I agree with you completely that the companies would not want to and should not involve themselves in the insurance process too. This attempt by Hough Ear Institute to involved themselves in the insurance process is even more stupid when the language used was 'may be covered by insurance.' This is no guarantee that the treatment actually will be covered by insurance. The same scenario of no guarantees on insurance coverage would definitely play out with FX-322.

 

Sorry if it’s been discussed, but will we need to go in once a year for more injections? Or is it a one and done kind of thing? And would they charge us for each additional shot?

Probably goes down to whether the regenerated hair cells hold the structural integrity of the originals.

 

The latest updates from Frequency Therapeutics included some durability results - the benefits persisted up to 21 months so it indicates that it could be a long-term treatment.

 

It would be very profitable for Frequency Therapeutics if they had annual repeat customers... but if it fixed my hearing issues for $1,000 a year it would be more then reasonable.

 

I believe David Lucchino (Frequency Therapeutics CEO) mentioned that getting bi-yearly "boosters" could be an option for some people. It was in one of the conferences he was in recently regarding the durability. It came as a question regarding the patients who dipped in WR score and if boosters were a possibility.

They would most likely charge for the booster shot. However, according to Wikipedia, progenitor cells can only replicate a certain number of times. It's unclear to me (and maybe everyone at this point?) how many times the ones in the ear can replicate.

 

I think that there is a very high chance that FX-322 will be a long-term treatment.

Apparently according to the information on progenitor cells the theory is that this results in actual permanent regrowth. The fact that treatment with FX-322 has proven that there is durability to date and the fact that providing a durable treatment is a key component of making FX-322 effective is a big sign that it is making excellent progress. Particularly since this is further proof that FX-322 is functioning further in line with how Frequency Therapeutics intended it to.

 

I'm not sure either how many times they can replicate but that is a great question.

Someone posted that deaf mice were cured... so that would mean many. Does anyone have a compiled list of information as to what FX-322 has proven to do up to this point?

x people saw 10 dB improvement at 8 kHz...
x people improved word recognition scores...
lab results on animals...
lab results on a human cochlea...

Right now the information is scattered throughout the thread.

I would love to be able to edit the first post with this info so that everyone can go to that and have the most recent information. I'm not sure if that is possible but it would be a great tool to keep everyone informed while allowing the conversations to keep going.

 

In terms of the annual shot concept that Lucchino shared; here is what I take of it:

New classifications of hearing "health" visits:
I think over the long-run, the consumers of FX-322 are going to fit in a few different classifications that will likely require return visits:

1. The Occupational Noise / Work-related patient:
People in construction, mining, motorsports, entertainment, military, or doing anything else where they are at high risk every day of accumulating hearing-loss. Many of these groups are already required to have annual visits once they are mid-late career and already realize they have a problem. With FX-322, employers may opt to have preventative visits take place, where hearing is checked and a quick "tune-up" is given; and they can return to work.

2. Age-related patient:
Now that we know Presbycusis is basically just SNHL from the recent publication from Mass Eye/Ear; people with this condition may also need to make regular visits as they continue to age. Since FX-322 replaces only dead/damaged hair cells, it's likely aged ones that still function may not be replaced. So, over the course of the next year-or-so, those "original equipment" aged cells may need replaced with another shot.

3. Recreational:
Speaking from experience, I personally think this group will be much more prominent that Frequency is currently estimating. These are the regular concert goers, sports enthusiasts, motorsports enthusiasts, gun enthusiasts, DIYers, headphones to loud etc. They'll come in complaining of hearing issues after an incident (like we all do), except in the post-FX-322 the ENT can give them a shot, and in a couple weeks, their hearing will be back to normal. The trouble here is, they probably won't learn their lesson, and will be back to doing the same old irresponsible thing with their hearing, and will be back again.

4. The Recovered:
This is all of us. People who have lived with tinnitus and hearing loss for years before FX-322 restored their hearing, and treated their tinnitus. While most here have had years to learn their lesson, and probably wont fall into 1 or 3; we may still need some on-going treatment as our ears heal. We will also likely be more sensitive than the others to changes in hearing, and will likely opt for care more often over the long term. I think this group will diminish over the long-long term, but for many years patients that have accepted the "permanence" of hearing loss will be much more apt to see their ENT if they know there's a way to keep their ears healthy.

 

Yeah I have a lot of problems with that Wikipedia article and its sources. The sources that reference the limitations of reproducing progenitors cite articles over 15 years old. It may very well be that the LGR5+ progenitors in our ears only can perform differentiation so many times; but it wont be known after years of treating patients what that range is.

I tried to use studies on birds as a reference to get an idea of perhaps how many times mammal ear progenitors might be able to "cycle" new IHCs/OHCs. There's not a whole lot I could nail down to show that it was 1-and-done for birds.

The good news is, we know that the LGR5+ in the gut seem to have no problem regenerating on a weekly basis.

 

We'll have to wait and see what the results are. I hope they can get meaningful hearing threshold improvements at high frequencies, not just above 8 kHz but also lower. We'll have to see about that. That would be a lifesaver for me. Either way, I know that one day I will get my hearing back one way or another. I just hope I'll be able to afford it!

 

If I look at the evidence correctly, the theory is that progenitor cells could and should become permanent, particularly since this is a key component of this treatment based off of the theories. The thing is that there may be some who will need booster shots for whatever reason, however I feel that over time the regrowth will become permanent and also stable.

One possible theory is that the volume of the medicine which benefitted certain areas wasn't enough to cause sufficient regrowth of the cells over time and therefore there was a short term gain which wasn't maintained in the long-term. Thus this tends to indicate to me much more that the regrowth will be maintained providing the cells get sufficient dosing. This is further evidence I think that the use of multiple doses will yield a much more meaningful benefit than just the single dose.

 

Will the hair cells go through an initial phase during regrowth where they are much more delicate and susceptible to injury because they haven't fully "solidified" to the cochlea, you think?

 

Nobody knows the answer to this question, unfortunately. I think the best indication is that there was some trial data stating improvement was maintained x number of months, though I forget how long it was exactly. Without more data it's just speculation imo.

 

Exactly. If this isn't a problem in the gut and the cochlea has the same sort of progenitor cell, I don't see why it would be a problem there.

 

Intuitively, I would think they'd be less prone to at least noise injury initially because they haven't fully made the synaptic connection yet. Or at least less prone to glutamate hyperexcitabilty.

 

It is interesting that there is seemingly a lot of medical material coming out recently which has happened to totally overturn what the previous position was. I think that we have seen this around ten years or so ago with the heart medicine and also again recently with a lot of this hearing stuff.

It seems a lot of doctors are still simply relying on or referring to the research which came out a long time ago particularly in relation to the hearing stuff. I think that medical researchers have proven a lot of things false recently and this is where the lack of knowledge and/or outdated views have come from.

I personally would trust the information that the researchers have been coming out with as they are fair more suited and far more knowledgeable than the knowledge of many doctors is. I am with you and think that there will be no problem with achieving this regrowth either.

 

Even if the progenitor cells have a limit to how many times they can be used, which according to the guys working intimately with them isn't the case, even having a handful of opportunities to regenerate lost hair cells is amazing.

For most people, it took decades of reckless abuse of the ears to make hearing loss noticeable. Yes, for many there was a straw that broke the camel's back but I bet there was decades of abuse previously.

I know that for myself, I would be so much more careful. For years now I've had earplugs attached to my keys so that I can wear them whenever I'm in a loud bar, concert or environment at work and that would continue after a successful injection of FX-322. That minor, continued lifestyle change would help minimize the ongoing damage to the point where I would likely not need to regrow any hair cells for 40 years! And same would go for most people here since I bet we would be so grateful of a second chance.

 

Just a quick glance at the other side of the world.

How are Astellas getting along?

Somehow I had in the back of my mind the notion of couch-surfing/crashing with some old mates of mine Stateside. But as far as I can tell, Frequency Therapeutics are not doing trials in the Twin Cities area .

But once it comes out on the market I figure it would be most economical to deliver the magic stuff to be injected over to each national country.

A few days back there were people in-the know expressing worries about the logistics of getting a possible COVID-19 vaccine delivered and distributed once it gets invented.
I wonder will we face the same problem?

 

There's good and bad everywhere. A friend of mine in Europe is a pharma referent. You know, sells pharmaceutical products to medical practices... but he is also informing the doctors of the latest developments.