Frequency Therapeutics — Hearing Loss Regeneration

[frpp]

192 days until we have answers, and about 4 years till we can finally sit in silence.

 

[tiredofit]

There are many kinds of inner ear dysplasias. Do you know which one you have?

Mondini is one type of dysplasia, for instance, that causes mixed losses and if that's what you have, it would be hard to say if FX-322 would be effective or not because you would have an abnormally large bony canal which would contribute to further pressure injury.

Enlarged Vestibular Aqueducts and Childhood Hearing Loss

In the case of Mondini OHCs are involved because otoacoustic emissions (which measure a range of OHC response specifically) can be normal at birth and then decline rapidly.

My thought on this is that, on one hand, you maybe could regain some of the SNHL portion of your losses (would not help your conductive losses of course) but you might be continually damaging your hair cells and possibly also they wouldn't regenerate properly with the pressure of the enlarged aqueduct (but I am not really sure).

This could be completely irrelevant to your particular dysplasia as well if it's another kind.

Is there an expert in your particular malformation you could consult? Any of us would just be speculating.

I do want to add that a lot of dysplasia sufferers are still cochlear implant candidates and CIs are improving and will greatly improve with optic (vs electrical) CIs.

I'm not completely sure, I will call tomorrow to get some info.

I'm not yet hard of hearing enough (profound) and not even sure I'd want CIs. I'm 24 and still into dating around, the only hearing aids that leave me a little bit of confidence are my in-ear hearing aids.

 

[tbuzz89]

4 years till we can finally sit in silence.

I would certainly hope that we don't have to wait four years.

 

[frpp]

I would certainly hope that we don't have to wait four years.

I hope not either but most likely FX-322 won't be out for at least 2 years, and likely more for OTO-413, plus add the time for either of these drugs to fully kick in. I figure 4 years is conservative, could be less if compassionate use is granted.

 

[Princebeyel]

192 days until we have answers, and about 4 years till we can finally sit in silence.

Gtfoh with your negativity! For real man, I don't need to see it. Some of us are optimistic and praying for a cure.

 

[frpp]

Gtfoh with your negativity! For real man, I don't need to see it. Some of us are optimistic and praying for a cure.

Not being negative, I'm praying for the same cure. 192 days is just the time for phase 2 to be over on May 21st, and notice I said 4 years till we can sit in silence meaning I'm positive that it works. Please don't jump the gun and snap at me.

 

[Princebeyel]

Not being negative, I'm praying for the same cure. 192 days is just the time for phase 2 to be over on May 21st, and notice I said 4 years till we can sit in silence meaning I'm positive that it works. Please don't jump the gun and snap at me.

I'm sorry man. I really am. I can't wait four years. I truly can not.

 

[Diesel]

I wanted to share something I learned from an acquaintance who had experience doing FDA-approved observational studies on patients at a local university hospital.

I asked him how Frequency Therapeutics could release data on the Phase 2A prior to its end date, and what that could mean in terms of their confidence in the data? The first thing he pointed to was the roles in the trial.

Here are the roles:

Sponsor: Frequency Therapeutics.
Patient: The trial participant.
Care Provider: Located at Clinical Trial Site; they gave the random "set" of FX-322/Placebo.
Outcome Assessor: May work at Clinical Trial site; runs the follow-up tests, records data, is usually rotated if assessing multiple patients.
Investigator: Carl LeBel of Frequency Therapeutics.

The job of the investigator is to conduct the trial, follow FDA protocols, maintain record keeping, maintain blinded data on participants in the investigation.

He mentioned that depending on the rolling reviews provided by the FDA, they may allow the Investigator to observe blinded data from the outcome assessor and report it back to the sponsor in an interim analysis.

So, Carl LeBel may have already received blinded 90-day data with approval from the FDA that didn't indicate what dosage level patients received, but did provide indication of outcomes.

His opinion was the data must look pretty good, even if totally masked mid-trial for them to get approval to push it out to the public early.

 

[weab00]

I'm sorry man. I really am. I can't wait four years. I truly can not.

Better than waiting 50 years to die or roping. Just imagine, of every generation with screaming tinnitus for the past 100,000 years, we're the first where curing it is a very real possibility.

 

[frpp]

I'm sorry man. I really am. I can't wait four years. I truly can not.

Ditto man. It feels like forever. Keeping my fingers crossed on compassionate use.

 

[HootOwl]

An OAE test can show the health of your hair cells.

I think these are pretty noisy though. I asked my audiologist about this once and he told me OAE tests are loud and he would not recommend it for anyone who's concerned about worsening their tinnitus.

 

[TrevorSanders]

I think these are pretty noisy though. I asked my audiologist about this once and he told me OAE tests are loud and he would not recommend it for anyone who's concerned about worsening their tinnitus.

In my experience, it was about as loud as earbuds at 50%.

 

[FGG]

I'm not completely sure, I will call tomorrow to get some info.

I'm not yet hard of hearing enough (profound) and not even sure I'd want CIs. I'm 24 and still into dating around, the only hearing aids that leave me a little bit of confidence are my in-ear hearing aids.

If a big issue for you is the cosmetic implications and/or potential negative attention from a cochlear implant, fully implantable CIs are coming very soon (next few years):

MED-EL: First Surgeries Ever in Europe with a Totally Implantable Cochlear Implant

 

[FGG]

Does anyone know if FX-322 might treat hearing loss caused by a head trauma? I read somewhere that an impact to the head can cause additional damage to the cochlea besides dead/damaged hair cells.

A quick intro: I am a 57-year-old male and endured a car driving into the left side of my head whilst on a cycle 24 years ago. I have suffered moderate hearing loss and mild tinnitus since then up until 4 weeks ago when overnight my tinnitus increased in volume and a new tone (low hum) manifested itself.

If your head trauma was 24 years ago, i wouldn't assume it's related (unless you have neck issues since or jaw misalignment in which case it might be).

From everything I have read, low tones often don't have the usual causes and it is worth a full work up to rule out things like hydrops, Eustachian Tube Dysfunction (which can even be a sequella of TMJ), perilymph fistula, etc etc.

If it's not hair cell related, Frequency won't help obviously but many other causes do have available treatments.

Tl;dr: see an otologist, an ENT subspecialist.

 

[Princebeyel]

Better than waiting 50 years to die or roping. Just imagine, of every generation with screaming tinnitus for the past 100,000 years, we're the first where curing it is a very real possibility.

I would definitely get cochlear implants before then. My problems are the hearing loss and word recognition. I can live with tinnitus even though it's excruciating at times.

 

[vttbx]

I think these are pretty noisy though. I asked my audiologist about this once and he told me OAE tests are loud and he would not recommend it for anyone who's concerned about worsening their tinnitus.

I have had two OAE tests while having reactive tinnitus and they never caused a spike.

But the one you want to avoid at all costs is the ABR test. Even at 80 dB (the lowest volume it can be used at), I feel like it damaged my hearing further.

 

[L34]

Acoustic trauma and noise induced hearing loss are the same thing. So far in the clinical trials they have got positive results and it shows it can restore your hearing and this was with 1 dose of FX-322

Thank you I had read somewhere (I don't remember exactly where) that it was two different things. So I had my doubts and difficulties trying to find out what is the cause of my tinnitus...

Another question...
Do we know how FDA looks at tinnitus? Do they consider it a serious condition, which destroys people's lives and makes you think about suicide, or do they just think it is a little noise, that can be tuned out when sitting and reading for instance? If it is the latter, then I don't believe in getting FX-322 for compassionate use... Anybody who knows more than me?

 

[Philip83]

Acoustic trauma and noise induced hearing loss are the same thing.

If one wants to split hairs (no pun intended) I think "acoustic trauma" usually adheres to a "bang" or a loud short sound, while "noise induced hearing loss" is if you're exposed to a relatively loud environment for a prolonged period of time, like working in a noisy factory, etc.

But yes, the "result" if you will, on your hair cells should be the same, and a remedy that combats one of these should logically also combat the other.

 

[L34]

If one wants to split hairs (no pun intended) I think "acoustic trauma" usually adheres to a "bang" or a loud short sound, while "noise induced hearing loss" is if you're exposed to a relatively loud environment for a prolonged period of time, like working in a noisy factory, etc.

But yes, the "result" if you will, on your hair cells should be the same, and a remedy that combats one of these should logically also combat the other.

Okay I understand, thanks! So the "result" is damaged hair cells and tinnitus. And the FX-322 seems to repair them... Fingers crossed...

 

[Diesel]

Another question...
Do we know how FDA looks at tinnitus? Do they consider it a serious condition, which destroys people's lives and makes you think about suicide, or do they just think it is a little noise, that can be tuned out when sitting and reading for instance? If it is the latter, then I don't believe in getting FX-322 for compassionate use... Anybody who knows more than me?

The FDA granting FX-322 the Fast Track Designation is an acknowledgment that they identify SNHL/NIHL as life-threatening or severely life-altering. Tinnitus is a symptom of SNHL/NIHL.

 

[L34]

The FDA granting FX-322 the Fast Track Designation is an acknowledgment that they identify SNHL/NIHL as life-threatening or severely life-altering. Tinnitus is a symptom of SNHL/NIHL.

Thank you @Diesel.

 

[HootOwl]

I have had two OAE tests while having reactive tinnitus and they never caused a spike.

But the one you want to avoid at all costs is the ABR test. Even at 80 dB (the lowest volume it can be used at), I feel like it damaged my hearing further.

Ah okay, my cochlea is so inflamed at this point even 70 decibel noise exposures has caused worsenings so perhaps I'm being overly cautious.

Like how some people have had MRIs with both ear plugs and muffs and even that wasn't enough protection, and their tinnitus spiked.

In my experience, it was about as loud as earbuds at 50%.

50% of my ear buds was actually still enough to irritate my hair cells and give me phantom sounds for a day... man I read responses like this and then I think are my ears just super fucked...

I think my experiences have just steered me in the direction of being too cautious, but it sounds like I'm probably in the minority when it comes to the extent of inflammation and sensitivity in my cochlea.

 

[tiredofit]

If a big issue for you is the cosmetic implications and/or potential negative attention from a cochlear implant, fully implantable CIs are coming very soon (next few years):

MED-EL: First Surgeries Ever in Europe with a Totally Implantable Cochlear Implant

Yeah I actually emailed them directly about it to try and be a test subject for the CI, they (he) said they are not taking in any more test subjects (forgot the word for it lol) but the CI shouldn't be in the market for another few years or so.

 

[tommyd87]

I wanted to share something I learned from an acquaintance who had experience doing FDA-approved observational studies on patients at a local university hospital.

I asked him how Frequency Therapeutics could release data on the Phase 2A prior to its end date, and what that could mean in terms of their confidence in the data? The first thing he pointed to was the roles in the trial.

Here are the roles:

Sponsor: Frequency Therapeutics.
Patient: The trial participant.
Care Provider: Located at Clinical Trial Site; they gave the random "set" of FX-322/Placebo.
Outcome Assessor: May work at Clinical Trial site; runs the follow-up tests, records data, is usually rotated if assessing multiple patients.
Investigator: Carl LeBel of Frequency Therapeutics.

The job of the investigator is to conduct the trial, follow FDA protocols, maintain record keeping, maintain blinded data on participants in the investigation.

He mentioned that depending on the rolling reviews provided by the FDA, they may allow the Investigator to observe blinded data from the outcome assessor and report it back to the sponsor in an interim analysis.

So, Carl LeBel may have already received blinded 90-day data with approval from the FDA that didn't indicate what dosage level patients received, but did provide indication of outcomes.

His opinion was the data must look pretty good, even if totally masked mid-trial for them to get approval to push it out to the public early.

I'm totally hopeful that this is indeed good news. I hope we will see beneficial, brilliant and significant outcomes.

 

[grate_biff]

I think my experiences have just steered me in the direction of being overly cautious, but it sounds like I'm probably in the minority when it comes to the extent of inflammation and sensitivity in my cochlea.

I'm on Prednisolone now. Hoping it will do something with an eventual inflammation in my cochlea or brain stem. I'm on it for a different reason though.

 

[Diesel]

I'm totally hopeful that this is indeed good news. I hope we will see beneficial, brilliant and significant outcomes.

My expectations after this conversation is that they have likely observed enough of a difference in outcomes after 90 days, that they may be able to infer who got Placebo, 1, 2 or 4 injections.

 

[FGG]

My expectations after this conversation is that they have likely observed enough of a difference in outcomes after 90 days, that they may be able to infer who got Placebo, 1, 2 or 4 injections.

Are you saying the data is still blinded but they would have a good speculation as to who got what?

Interesting. And that would explain a lot.

 

[Philip83]

My expectations after this conversation is that they have likely observed enough of a difference in outcomes after 90 days, that they may be able to infer who got Placebo, 1, 2 or 4 injections.

Is anything known about how long it takes before the benefits kick in after you get the injection? Does it take days or weeks to see improvements?

 

[Diesel]

Are you saying the data is still blinded but they would have a good speculation as to who got what?

Interesting. And that would explain a lot.

That's my understanding. The Outcomes Assessor is blind to whom received Placebo, 1,2,4 doses. They should know what site they participated in, but they may not know their baseline/day 0 assessment. They also have data on the progression of improvements (or lack there of).

The interim analysis provided to the Investigator could have consisted of a straight snapshot of all participants at 90 days; without reference to their baseline, and what facility they where they were treated. This keeps the investigator blind to their initial acceptance criteria of the patient.

It probably looked like an exported table like so:

DAY 90 Data:

 

[Diesel]

Is anything known about how long it takes before the benefits kick in after you get the injection? Does it take days or weeks to see improvements?

Based on the word score improvements from the Phase 1/2, looks like after 2 weeks improvements seem to be noticeable. May change with more injections.