Frequency Therapeutics — Hearing Loss Regeneration

[TrevorSanders]

That's interesting.

CHIR99021 retails for est. $30 /1mg
Valproate Sodium est. $3 / 1mL

So if FX-322 is equal parts Valproate Sodium and CHIR99021, at retail prices we're looking at... what?

$500 for the shot and $5,000 for the ENT visit.

 

[Aaron91]

$500 for the shot and $5,000 for the ENT visit.

At least they'll actually be earning their money for once.

 

[Drachen]

That's interesting.

CHIR99021 retails for est. $30 /1mg
Valproate Sodium est. $3 / 1mL

So if FX-322 is equal parts Valproate Sodium and CHIR99021, at retail prices we're looking at... what?

Alright folks, you know the drill. Time to fire up those back alley clinics and get to manufacturing!

 

[FGG]

Alright folks, you know the drill. Time to fire up those back alley clinics and get to manufacturing!

Won't work unless you know a back alley otologist to give it to you.

 

[TrevorSanders]

At least they'll actually be earning their money for once.

For real man. Can't believe they can put a $300 price tag on "Tinnitus? Deal with it".

 

[Guywithapug]

@Drachen, what a deal! Thanks for confirming the final price for FX-322 lol. If it does show good efficacy, I'd be willing to take out some sizeable loans if that's what it takes...

I thought you might get a kick out of my new avatar.

 

[Jrblovsky]

I don't see the price being too outrageous. The hearing aid market is about to get a lot more competitive since over-the-counter hearing aids will be coming within the next few years. This will mean FX-322 won't just be competing against prescription hearing aids, which can cost $2k+, but with ones more affordably priced at maybe $100 (and no doctor visit!). Plus there's speculation that brands like Apple will be entering this market.

So if FX-322 were to cost $20k per injection, almost no one would get it when they could instead get a $1k Apple hearing aid. I think the market will basically force them to make the price reasonable (my gut is $1k per injection). Plus, if these market forces fail, there's still OTO-6XX on the horizon, which will provide direct competition.

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

 

[Drachen]

Won't work unless you know a back alley otologist to give it to you.

How hard can it be? Just take needle + stick into ear + push in goo + don't swallow = easy.

I thought you might get a kick out of my new avatar.

Marvelous! We classy hounds have to stick together.

 

[Drachen]

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

From Wikipedia for Dexamethasone:
"In 2017, it was the 321st most commonly prescribed medication in the United States, with more than one million prescriptions."

From an NIH article on hearing loss in America:
"Approximately 15% of American adults (37.5 million) aged 18 and over report some trouble hearing."

And that's just adults who have "reported" trouble hearing in 2012. This doesn't account for the likely many, many more with some degree of hidden hearing loss, nor does it account for the likely noteworthy increase in hearing loss affecting newer generations due to overuse of electronic devices and concert attendance.

The much greater market and ease of ability in producing this drug is going to ensure it's not prohibitively expensive. It's most likely not going to be what most would consider cheap, but it will be reasonably priced (as far as pharmaceuticals go) if Frequency Therapeutics want to make the most money they can.

 

[Diesel]

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

If that's the case, so many drugs that are covered today wouldn't be.

Word score (WR/WIN) and QOL are looking like the measurements that will be pushed to insurance providers to get coverage.

Pure Tone Average improvement by % may be a secondary measure. So bringing a patient's average from moderate to mild levels overall.

I say QOL because many MS, HIV, and other drugs do end up covered because quality of life improvements correlate over the long term with a less expensive cost to insurer.

 

[Guywithapug]

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

I'm thinking the same, if it actually works, there is a huge market and if premium level hearing aids cost $4-5k, they could charge somewhere in that range. OTC hearing aids just don't have the same technology nor are they tailored to the individual's hearing. You also have to get hearing aids replaced periodically and not everyone likes the aesthetics of them.

It also can't be absurdly expensive, otherwise they wouldn't tap into as much of the market as they potentially could. If I were to take a stab at a rough price, I'd say between $1800-$2500.

 

[Jrblovsky]

I'm thinking the same, if it actually works, there is a huge market and if premium level hearing aids cost $4-5k, they could charge somewhere in that range. OTC hearing aids just don't have the same technology nor are they tailored to the individual's hearing. You also have to get hearing aids replaced periodically and not everyone likes the aesthetics of them.

It also can't be absurdly expensive, otherwise they wouldn't tap into as much of the market as they potentially could. If I were to take a stab at a rough price, I'd say between $1800-$2500.

If it restores natural hearing, it will be way more than that. I can assure you that regardless of how premium a hearing aid is, it does not sound like your natural hearing. I trialed a Phonak top of the line model for four months. It does help with speech but it still doesn't bring back how I used to hear. I have a pretty good comparison being my other ear works correctly with no hearing loss or tinnitus.

They could charge $50,000 and I would pay it. The quality of life hearing loss has taken from me is worth that easily.

 

[TrevorSanders]

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

If that's the case, just fake a hearing test and make it seem like you have hearing loss in some of the frequencies tested.

 

[Gb3]

An injection of Dexamethasone is over $1,000. FX-322 will be expensive. If it actually works, then I would find a way to pay for it. If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

Dexamethasone isn't even proven to work for sudden hearing loss and it was covered by my insurance. I had four injections.

 

[Guywithapug]

If it restores natural hearing, it will be way more than that. I can assure you that regardless of how premium a hearing aid is, it does not sound like your natural hearing. I trialed a Phonak top of the line model for four months. It does help with speech but it still doesn't bring back how I used to hear. I have a pretty good comparison being my other ear works correctly with no hearing loss or tinnitus.

They could charge $50,000 and I would pay it. The quality of life hearing loss has taken from me is worth that easily.

I'm in the same boat as you, hearing loss in the left ear, while the right ear is still good.

I think the expectation of restoring natural hearing may be a little optimistic though, it may improve our current hearing but to completely restore it to how it was before seems a little unrealistic. I really do hope I'm wrong but time will tell.

Like you, I'd be willing to pay a lot to hear better again and lower/eliminate the tinnitus for sure.

But that is something that concerns me, them knowing that we're desperate and taking full advantage of our situation by charging an insane amount of money when results would surely vary by individual cases.

 

[Jrblovsky]

Maybe I'm wrong. I just know everything I've tried to do with insurance has been a huge ordeal and they deny everything. Hopefully the clinical trials they are doing now show actual results and then they will for sure cover it.

 

[Diesel]

I'm in the same boat as you, hearing loss in the left ear, while the right ear is still good.

I think the expectation of restoring natural hearing may be a little optimistic though, it may improve our current hearing but to completely restore it to how it was before seems a little unrealistic. I really do hope I'm wrong but time will tell.

Like you, I'd be willing to pay a lot to hear better again and lower/eliminate the tinnitus for sure.

But that is something that concerns me, them knowing that we're desperate and taking full advantage of our situation by charging an insane amount of money when results would surely vary by individual cases.

This is why QOL is such an important measure. If you feel like your hearing is "back to the way it was", then no hearing test will show that, but QOL will be the best indicator.

The way they are positioning the product, and describing how it fits into the current treatment workflow doesn't make it look like a 5-figure drug per dose. Typically infusions get into that level for cancer, MS, et al.

Multiple injections may get into the 5-figures, but it will depend on the damage needing treatment IMO.

Stockholders will want mass volumes of the drug in ears around the world at all times, not a premium drug for a high-income market.

 

[Drachen]

Multiple injections may get into the 5-figures, but it will depend on the damage needing treatment IMO.

So are you thinking extensive damage will need to warrant multiple injections primarily?

There is still that lingering concern regarding getting to the lower frequencies. Specifically, I am interested about that 4-8 kHz range, which is still a bit down the cochlea, and it's even worse for those who may need them lower.

 

[wwtsai]

They could charge $50,000 and I would pay it. The quality of life hearing loss has taken from me is worth that easily.

Agreed. A return to normalcy or near normalcy is priceless for me at this point.

 

[Jrblovsky]

Dexamethasone isn't even proven to work for sudden hearing loss and it was covered by my insurance. I had four injections.

It doesn't do anything for me anymore either. It used to help a little and I had the injections done every 60 days. The ENT I was seeing dismissed me, saying he cannot figure out what is wrong.

 

[Diesel]

So are you thinking extensive damage will need to warrant multiple injections primarily?

There is still that lingering concern regarding getting to the lower frequencies. Specifically, I am interested about that 4-8 kHz range, which is still a bit down the cochlea, and it's even worse for those who may need them lower.

I am speculating that if they think that multiple doses push the drug lower into the frequency range, than multiple doses will be needed in a short period of time to get the concentration high enough to have an effect.

The Phase 2A may help confirm this.

Ex: If we find out that 2x doses show improvements at 4 kHz on the audiogram, then if a patient comes in with losses focused specifically at 5 kHz - 7 kHz, then the doctor will need to "dose up" the FX-322 concentration in the cochlea to diffuse into that range.

 

[Jrblovsky]

I am speculating that if they think that multiple doses push the drug lower into the frequency range, than multiple doses will be needed in a short period of time to get the concentration high enough to have an effect.

The Phase 2A may help confirm this.

Ex: If we find out that 2x doses show improvements at 4 kHz on the audiogram, then if a patient comes in with losses focused specifically at 5 kHz - 7 kHz, then the doctor will need to "dose up" the FX-322 concentration in the cochlea to diffuse into that range.

Hopefully you're right and it shows gains in speech frequencies.

 

[paul mclean]

I reckon it'll be around $1,000 per week of treatment, split 50/50 between the drug and ENT.

The drug is cheap to make but ENTs will definitely want their share. The procedure takes 15 minutes in office so it isn't a huge deal.

If you need 4-5 weeks for noticeable change, then they will be making at least $5,000 off each patient which is the same price as some hearing aids.

They can't really afford to make it exorbitantly priced.

 

[Dolgoruki]

If it doesn't affect the frequencies that are typically tested, I can 100% guarantee you that insurance companies won't be paying for it.

Hopefully they can get the dosing right and show actual results. Like 50 or 60 decibel gains in all frequencies.

FX-322 has shown results in word recognition scores. Isn't that a function of hearing health at lower frequencies, and already proof that FX-322 can be beneficial also for the lower frequencies?

I have mild hearing loss in the 4 kHz - 5 kHz range so I really hope that is in fact the case...

 

[vermillion]

None of the synaptopathy drugs will likely come out around the time of FX-322 with the exception of OTO-413 possibly. OTO-413 is just injectable BDNF.

Reading that, I recalled the following publication of Prof. Liberman:

Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure

Specifically the following worrisome sentence caught my attention:

"...Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability..."​

If I got this right, the number of years, during which this approach could work, is quite vague.

Now in my case that I reached my 4th year mark, considering the above statement and given the fact that OTO-413 will take several more years to reach the market (if so), shall I sadly assume that it won't be an option for me and for others, since those neurons possibly won't have survived by that time?

 

[FGG]

Reading that, I recalled the following publication of Prof. Liberman:

Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure

Specifically the following worrisome sentence caught my attention:

"...Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability..."​

If I got this right, the number of years, during which this approach could work, is quite vague.

Now in my case that I reached my 4th year mark, considering the above statement and given the fact that OTO-413 will take several more years to reach the market (if so), shall I sadly assume that it won't be an option for me and for others, since those neurons possibly won't have survived by that time?

I wish I could find the reference again (it's in here somewhere if you want to dig) of a study that was published since, but it turns out that's just for rodents. In humans, based on autopsy studies, that process takes decades if at all.

 

[serendipity1996]

Reading that, I recalled the following publication of Prof. Liberman:

Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure

Specifically the following worrisome sentence caught my attention:

"...Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability..."​

If I got this right, the number of years, during which this approach could work, is quite vague.

Now in my case that I reached my 4th year mark, considering the above statement and given the fact that OTO-413 will take several more years to reach the market (if so), shall I sadly assume that it won't be an option for me and for others, since those neurons possibly won't have survived by that time?

I'm pretty sure it's been established that this therapeutic window tends to persist for decades. @FGG is more well-versed on this than I am.

 

[vermillion]

I wish I could find the reference again (it's in here somewhere if you want to dig) of a study that was published since, but it turns out that's just for rodents. In humans, based on autopsy studies, that process takes decades if at all.

Do you mean to dig it in the PubMed journal?
I can try to do that but it will take time.

I'm pretty sure it's been established that this therapeutic window tends to persist for decades. @FGG is more well-versed on this than I am.

Thank you @serendipity1996.
I'll try to track this down.

 

[Diesel]

FX-322 has shown results in word recognition scores. Isn't that a function of hearing health at lower frequencies, and already proof that FX-322 can be beneficial also for the lower frequencies?

I have mild hearing loss in the 4 kHz - 5 kHz range so I really hope that is in fact the case...

About half of the words in English rely on a syllable in the high frequency range to be effectively understood. I suspect that the dramatic increase in word score was from those high frequency hair cells being mostly restored.

What we know is that on the audiogram, patients saw a 10-15 dB improvement at the 8 kHz pure tone. However, the audiogram fails to tell us where exactly the participant stopped seeing a benefit from FX-322 down to the 4 kHz tone, where none saw a gain. So, they could have seen gains at 7 kHz, 6.4 kHz, 5.7 kHz, 4.2 kHz.

I can't recall who shared the research many pages ago, but it explained how crucial Inner Hair Cells are to recognizing parts of speech. Unfortunately the audiogram is a really terrible tool for measuring Inner Hair Cell performance. So, with this known, it's possible FX-322 did get deeper into the cochlea and caused the regeneration of Inner Hair Cells but not Outer Hair Cells. Perhaps from a biological standpoint, the Inner Hair Cells are regenerated first, or the body prefers to regenerate them first? At any rate, this may also explain the substantial word score improvement and lacking audiogram improvement.

 

[Diesel]

Reading that, I recalled the following publication of Prof. Liberman:

Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure

Specifically the following worrisome sentence caught my attention:

"...Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability..."​

If I got this right, the number of years, during which this approach could work, is quite vague.

Now in my case that I reached my 4th year mark, considering the above statement and given the fact that OTO-413 will take several more years to reach the market (if so), shall I sadly assume that it won't be an option for me and for others, since those neurons possibly won't have survived by that time?

So far no mention of a therapeutic window has been established for either drug. In fact, Chris Loose at Frequency Therapeutics mentioned in a past interview that the Phase 1/2 specifically targeted patients with a history of hearing loss and established relationship with their ENT. So, that tells me these patients that saw improvement had been living with hearing loss for years.

Secondly, the age-related hearing loss Phase 1b trial is set to end in Q2. This should reaffirm that patients who have likely had hearing loss for DECADES were still responders to the treatment.