Frequency Therapeutics — Hearing Loss Regeneration

[Lucifer]

Yeah this is what I mean. We should be focusing on initial approval regardless of whether the current combo reaches all the frequencies we want.

They will end up reformulating either way because the technology exists and multiple shots per ear is damn inconvenient for everyone. At that point we'll see the inner ear distribution we're looking for.

Since they already showed in both Phase 1b trials that there was an improvement in hearing and if the age-related hearing loss also shows improvement in hearing even though the severe hearing loss trial may not look as good, the FDA should allow them to go to the pivotal phase with their current delivery method as it will help millions of people who suffer from mild-moderate hearing loss. Just let FX-322 get the minimal approval and work on new delivery method later.

Why should mild-moderate hearing loss sufferers need to wait even longer due to the severe hearing loss trial not showing meaningful improvements. Lets get the minimal approval.

 

[FGG]

I realize that faking the word recognition test is the issue here, not the pure tone audiometry, but I wonder why FREQ did not use an OAE test (in addition to all the other tests). As I understand it, OAEs are used for infants who cannot communicate, and with adults for legal situations when it is important to know that the person is not faking a hearing loss (for example with a disability claim).

Easy to Google about OAEs, here is one site with a good overview:

"Many audiology clinics have added OAE to the standard battery of tests that they perform on every ear/hearing patient. Since patient participation is not needed, the results are completely objective."

"If the audiogram indicates a hearing loss, but the OAE and the pure tone audiogram do not agree, the patient may be malingering (faking a hearing loss)."

http://blog.e3diagnostics.com/oae-testing-and-the-standard-audiological-test-battery

OAEs don't go to the EHF. And participants couldn't have faked the standard audiogram because that was used to prove stability.

Ironically if the EHF audiogram was standard practice, then it would have mostly eliminated even that potential.

 

[Lucifer]

The age-related hearing loss trial of 65 years old or greater should be a clear indicator if FX-322 works or not. The likelihood of old people faking their hearing test is low. If it shows old people improving their hearing I can't see the FDA not allowing FX-322 to go to the pivotal phase at the beginning of next year.

They should consider releasing the drug while in the pivotal phase to those in the military.

 

[Tezcatlipoca]

I've flipped, in the sense that I have more faith in OTO-313 and SPI-1005 than I do FX-322 for more immediate relief of tinnitus.

I still intend on being a bear for those drugs. I need to study them.

You and me brother, I am always positive but deep down I know we are in it for the long run.

May you, me and everyone on this forum pop Ebselen like candy and get the OTO-313 injection in a couple of years!

 

[Still-Hope]

It really hurts...

 

[Christine2222]

I realize that faking the word recognition test is the issue here, not the pure tone audiometry, but I wonder why FREQ did not use an OAE test (in addition to the other tests). As I understand it, OAEs are used for infants who cannot communicate, and with adults for legal situations when it is important to know that the person is not faking a hearing loss (for example with a disability claim).

Easy to Google about OAEs, here is one site with a good overview:

"Many audiology clinics have added OAE to the standard battery of tests that they perform on every ear/hearing patient. Since patient participation is not needed, the results are completely objective."

"If the audiogram indicates a hearing loss, but the OAE and the pure tone audiogram do not agree, the patient may be malingering (faking a hearing loss)."

http://blog.e3diagnostics.com/oae-testing-and-the-standard-audiological-test-battery

My understanding is that there are limitations on what frequencies OAE tests can measure. This would have been interesting data for them to gather though because OAE tests are typically very consistent between tests.

 

[Tezcatlipoca]

Since they already showed in both Phase 1b trials that there was an improvement in hearing and if the age-related hearing loss also shows improvement in hearing even though the severe hearing loss trial may not look as good, the FDA should allow them to go to the pivotal phase with their current delivery method as it will help millions of people who suffer from mild-moderate hearing loss. Just let FX-322 get the minimal approval and work on new delivery method later.

Why should mild-moderate hearing loss sufferers need to wait even longer due to the severe hearing loss trial not showing meaningful improvements. Lets get the minimal approval.

A minimum viable product (MVP) is a version of a product with just enough features to be usable by early customers who can then provide feedback for future product development.

Minimum viable product

 

[Christine2222]

You and me brother, I am always positive but deep down I know we are in it for the long run.

May you, me and everyone on this forum pop Ebselen like candy and get the OTO-313 injection in a couple of years!

I would like to see Sound Pharmaceuticals offer compassionate use for this drug to people with severe tinnitus and hyperacusis.

 

[Zugzug]

The age-related hearing loss trial of 65 years old or greater should be a clear indicator if FX-322 works or not. The likelihood of old people faking their hearing test is low. If it shows old people improving their hearing I can't see the FDA not allowing FX-322 to go to the pivotal phase at the beginning of next year.

 

[Gb3]

It works in single dose trials. The drug "didn't work" when they poked multiple holes in people's ear drums day after day. Cochlear hair cells are nerves and nerves take months to years to completely heal. I think it was irresponsible on FREQ's part to have a trial where you inject the patient 4 days in a row. Injections 3 to 6 months apart would have been much more reasonable.[/QUOTEi

I'm sure they didn't poke multiple holes. The hole takes a while to heal and they go through the same one. This is what they did for me with steroid injections over four weeks one week apart.

 

[lymebite]

OAEs don't go to the EHF.

I personally have had a DPOAE test that went up to 10 kHz. I realize that's far short of 20 kHz but at least it's a bit higher than the standard 8 kHz.

Having had a DPOAE test once, and the standard audiometry test endless times, I wish they would give me the DPOAE every time, I feel like it is good additional information and it takes minimal additional time and effort by the audiologist. And minimal effort by me, since I don't have to listen for tones and push the button, it is all passive like getting a blood draw.

I do realize that it would in no way get to the core issues of the flaws in the FREQ test design, but it seems like it would provide at least one element of test results with ZERO patient subjectivity, and would do so for fairly negligible time and cost.

 

[Aaron91]

I think we've exhausted the post-mortem until we can get further data.

Suffice to say we're all devastated by this; I know I am, I had a lot riding on this. I think I may take a break from the forum for a week or two, this has hurt a lot.

 

[lymebite]

The likelihood of old people faking their hearing test is low.

Why do you think it is low?

I would guess the likelihood of older people faking is equal to or possibly higher than the likelihood of younger people faking. I know some people well over age 65 who are beyond desperate to improve their hearing and would do just about anything to make that happen. People who have lived a long time have been around the block a number of times and have learned how to game various systems.

 

[FGG]

I've flipped, in the sense that I have more faith in OTO-313 and SPI-1005 than I do FX-322 for more immediate relief of tinnitus.

I still intend on being a bear for those drugs. I need to study them.

At best, assuming Phase 2 were the liars and not Phase 1 (or FREQ), Frequency Therapeutics will likely have to run another Phase 2, which means it would be behind both of those drugs, for sure.

It would potentially put FX-322 within two years of OTO-6xx, too.

I guess it's possible with great results from the severe arm, for instance, they could do a Phase 2/3 but I would expect at least some sort of delay anyway in planning a way better trial.

 

[lymebite]

My understanding is that there are limitations on what frequencies OAE tests can measure.

I am no expert on OAEs, just a patient. But with my own OAE, they measured a total of 28 frequencies, at roughly even intervals, between 1 kHz and 10 kHz. With my standard pure tone tests, they typically check only 9 frequencies between 0.125 kHz and 8 kHz.

So, my OAE did not check the really low frequencies under 1 kHz, but it checked far more frequencies above 1 kHz than the standard audiometry tests. 28 seems a lot better than 9.

 

[Zugzug]

At best, assuming Phase 2 were the liars and not Phase 1 (or FREQ), Frequency Therapeutics will likely have to run another Phase 2, which means it would be behind both of those drugs, for sure.

It would potentially put FX-322 within two years of OTO-6xx, too.

I guess it's possible with great results from the severe arm, for instance, they could do a Phase 2/3 but I would expect at least some sort of delay anyway in planning a way better trial.

And that's assuming the other drugs don't run into roadblocks.

I'm pretty crushed. I never thought FX-322 would make or break my problem, but it's just so depressing how easy it is for these drugs to fail. I think, best case scenario, SPI-1005 provides me with a small treatment. If there even is a cure in my lifetime for my problem, it probably comes at an age where I die of cancer anyways or something.

I feel so bad for people following this thread with pathology where a successful FX-322 treatment would clearly help them. My natural tendency is actually to be a bear. It's kind of funny, I almost became a bull by surprise. A whole bunch of bear questions led me to reading more and more and I actually turned into a bull, to my own surprise.

I really can't believe that we actually have to worry about something like entry standards. That's such a small part of the whole process. Then there's the nightmare of the fact that Frequency Therapeutics is first trying to address EHF hearing loss, but with all 1940s hearing tests that aren't concerned with it. They have to toe a line between what their science can actually do and what's mainstream. All of the other drugs will face this same challenge -- probably why OTO-413 is redoing Phase 1/2.

Just really bad stuff.

 

[Lucifer]

View attachment 44236

Why do you think it is low?

I would guess the likelihood of older people faking is equal to or possibly higher than the likelihood of younger people faking. I know some people well over age 65 who are beyond desperate to improve their hearing and would do just about anything to make that happen. People who have lived a long time have been around the block a number of times and have learned how to game various systems.

More likely to have hearing issues the older they get. The clinical trial requires participants to be 65 years or older to enter. They would have most likely have had hearing damage over the years if they worked at places that are loud e.g military, police or factories.

I think depending on how their hearing issues started in the first place would be the best way of knowing if someone is lying or not about their hearing tests e.g did they attend a lot of concerts when they were younger or worked in roles with loud noise.

 

[Philip83]

At best, assuming Phase 2 were the liars and not Phase 1 (or FREQ), Frequency Therapeutics will likely have to run another Phase 2, which means it would be behind both of those drugs, for sure.

It would potentially put FX-322 within two years of OTO-6xx, too.

I guess it's possible with great results from the severe arm, for instance, they could do a Phase 2/3 but I would expect at least some sort of delay anyway in planning a way better trial.

Like I think has been discussed here before, I feel that since the safety profile is good across the board, and if FREQ is definitively able to prove efficacy in some patients (without knowing why some see improvement and some don't), wouldn't that be enough to make it to market as a first version? People would be able to try it. For some it might work, for some it doesn't. FREQ makes some money in the process and can keep improving the drug.

I'm pretty sure there are cancer treatments like this, who has very individual and random results, but aren't harmful. When my grandma had terminal cancer she got some drug like that, I remember.

 

[Lucifer]

At best, assuming Phase 2 were the liars and not Phase 1 (or FREQ), Frequency Therapeutics will likely have to run another Phase 2, which means it would be behind both of those drugs, for sure.

It would potentially put FX-322 within two years of OTO-6xx, too.

I guess it's possible with great results from the severe arm, for instance, they could do a Phase 2/3 but I would expect at least some sort of delay anyway in planning a way better trial.

I don't think they will have to do another Phase 2a trial as they have done numerous clinical trials with one dose of FX-322 showing that there is improvement in word scores. They have had over 200 participants in the clinical trials they have conducted.

If the age-related hearing loss trial shows meaningful improvements but the severe hearing loss category only showing little or no improvements this may be enough for FX-322 to go to a pivotal phase early next year.

If it helps mild-moderate sufferers with one dose of FX-322 why should they suffer longer cause the severe hearing loss category showed minimal or no improvements at all. I hope the FDA will be lenient and allow them to continue with the pivotal phase with the current delivery method and work on a new delivery method after Fx-322 is out so they can target lower frequencies so severe hearing loss sufferes can show meaningful improvements.

 

[Bill Arsenault]

In the meantime, there is no scenario where one of the 3 groups isn't lying unless you believe the placebo effect can double word scores (I don't).

Was there even any way that an extremely knowledgeable individual and talented con could have "successfully" lied their way through the trial? Meaning they were able to get access to treatment without getting caught and officially corrupting the results.

I mean, some tests just inherently can not be cheated on. Or would it have been child's play for someone with strong motivation and dedication?

Just trying to put myself in their shoes.

I get the whole having agonizing deafness/tinnitus and then being offered early access to potential relief.

It's the incredible stress of actually perpetuating a charade at that level while suffering- that has me baffled. Having to continually look a specialist in the eye and convincingly lie to them — all the while knowing damn well your messing with countless lives.

My take is that there were plenty of liars and they all have toys in the attic and live somewhere over the rainbow.

 

[Gb3]

At best, assuming Phase 2 were the liars and not Phase 1 (or FREQ), Frequency Therapeutics will likely have to run another Phase 2, which means it would be behind both of those drugs, for sure.

It would potentially put FX-322 within two years of OTO-6xx, too.

I guess it's possible with great results from the severe arm, for instance, they could do a Phase 2/3 but I would expect at least some sort of delay anyway in planning a way better trial.

This sucks, all because of people who were desperate enough to lie to get into the trial. When I called about the trial I even told them I don't think I would qualify because my word score was high.

 

[Zugzug]

Was there even any way that an extremely knowledgeable individual and talented con could have "successfully" lied their way through the trial? Meaning they were able to get access to treatment without getting caught and officially corrupting the results.

I mean, some tests just inherently can not be cheated on. Or would it have been child's play for someone with strong motivation and dedication?

Just trying to put myself in their shoes.

I get the whole having agonizing deafness/tinnitus and then being offered early access to potential relief.

It's the incredible stress of actually perpetuating a charade at that level while suffering- that has me baffled. Having to continually look a specialist in the eye and convincingly lie to them — all the while knowing damn well your messing with countless lives.

My take is that there were plenty of liars and they all have toys in the attic and live somewhere over the rainbow.

Which is why I don't think it's that many. The open-label Phase 1b only saw 34% of treated ears improve absolute WR by >=10%. This statistic is less affected by the ceiling effect because it's categorical and the "response" binary is a fixed, absolute number. It's also not placebo controlled, meaning its success would only be used as a kicker along with the other Phase 1b trials succeeding. It's not pushing this to Phase 3.

The two remaining Phase 1b trials would have to rock my socks off for me to believe that deceit killed the Phase 2a. Even then, what about PTA? Drug still sucks for OHC in every test.

The silver lining is that there probably are hardcore responders at one dose. But I wouldn't count on moving to pivotal without a redo of Phase 2 with better design.

 

[Tezcatlipoca]

Like I think has been discussed here before, I feel that since the safety profile is good across the board, and if FREQ is definitively able to prove efficacy in some patients (without knowing why some see improvement and some don't), wouldn't that be enough to make it to market as a first version? People would be able to try it. For some it might work, for some it doesn't. FREQ makes some money in the process and can keep improving the drug.

I'm pretty sure there are cancer treatments like this, who has very individual and random results, but aren't harmful. When my grandma had terminal cancer she got some drug like that, I remember.

Exactly, people act like drugs have to be perfect to be out, newsflash they don't!

Like you said, there's countless cancer drugs/treatments but 0 of them cure cancer.

 

[Lucifer]

Like I think has been discussed here before, I feel that since the safety profile is good across the board, and if FREQ is definitively able to prove efficacy in some patients (without knowing why some see improvement and some don't), wouldn't that be enough to make it to market as a first version? People would be able to try it. For some it might work, for some it doesn't. FREQ makes some money in the process and can keep improving the drug.

I'm pretty sure there are cancer treatments like this, who has very individual and random results, but aren't harmful. When my grandma had terminal cancer she got some drug like that, I remember.

I hope that is the case since they have had over 200 participants in the clinical trials and had no side effects, have showed improvements in word scores in Phase 1b with one dose of FX-322.

If the age-related hearing loss trial shows hearing improvements as well, then the FDA should allow them to go to the pivotal phase with their current delivery method and work on a new delivery method after FX-322 is out in the market.

 

[Zugzug]

Exactly, people act like drugs have to be perfect to be out, newsflash they don't!

Like you said, there's countless cancer drugs/treatments but 0 of them cure cancer.

Trust me, we are not in danger of FX-322 being perfect lol.

I share the sentiment with Compassionate Use. The problem is that while severe tinnitus and hyperacusis are very serious medical conditions, the FDA does not view it like cancer.

They can't put a hearing drug out on the market where efficacy proof is essentially a few anecdotes. What if, by chance, the people with massive word score improvements moronically deflated their baseline scores so that they could prove to the world that FX-322 worked? This sounds stupid, but human beings are stupid.

Then there's the issue of long-term safety outcomes, some risk of tympanic perforations, some risk of damaging the cochlea, educating people to administer the drug when there isn't even proof that it works well.

Regardless, if these conditions were viewed like cancer, heaven and earth may be moved. But this isn't happening, unfortunately.

 

[Lucifer]

Exactly, people act like drugs have to be perfect to be out, newsflash they don't!

Like you said, there's countless cancer drugs/treatments but 0 of them cure cancer.

The first drug that comes out in the market for hearing loss may not be perfect but if it has shown meaningful improvements in mild or moderate hearing loss sufferers then it should be able to go to the pivotal phase followed by market release.

 

[GlennS]

Having trouble clearing the time to scan through so many posts.

Could someone encapsulate what happened so I can bookmark the post?

I am hoping the Tinnitus Talk Podcast goes over it at least.

 

[knickfan]

I was in both Phases (1 & 2) of the trial for SPI-1005.

I have had Meniere's since 2008. I was diagnosed at 28. I have had tinnitus every day since. Ironically... tinnitus is the easiest symptom of Meniere's to deal with. Projectile vomiting from vertigo in ambulances was a doozy.

Hopefully Dr. Kil gets through the Phase 3 soon. It is a drug that will help a lot of people. I got the goods in Phase 1 and the placebo Phase 2.

I have been tracking FREQ like the rest of you. Watched the stock go from $55 to $8 like you too. I took a bath.

It is encouraging that they are not giving up. I think they will try to improve the delivery.

The fact four shots of liquid (turning into a gel) did not improve hearing DID NOT surprise me. Having that much liquid in your ear would HURT your scores on hearing tests. There is no where for the liquid/gel to go. I know... I lived with liquid in my ears for years until I got a Gentamicin shot.

They need to try one shot... somehow figure out a way for it to penetrate deeper into the cochlea... maybe use magnets.

Any case... hang in there folks... they will figure it out!!!

 

[Street Novelist]

I refuse to believe that after all the years it took to design FX-322, test it in vitro, and now in vivo, it doesn't work. That would mean either,

a: FX-322 is a failure and Frequency Therapeutics just wasted their time, or

b: the science behind all of this is false and it's not possible to regenerate hearing.

 

[Tezcatlipoca]

I was in both Phases (1 & 2) of the trial for SPI-1005.

Did it help with the tinnitus? What about the vertigo?