Frequency Therapeutics — Hearing Loss Regeneration

[weab00]

May I refer you to a graphic a wise person posted a few pages ago

View attachment 42077

 

[Philip83]

I'd like to point out that Frequency Therapeutics has been adding more marketing focused on Hearing In Noise, including today's Twitter post.

I find this interesting since the Phase 1/2 words-in-noise improvements weren't particularly compelling.

I wonder if they've seen more significant improvements from the long-term study patients, or already know they're going to see improvements in the upcoming Phase 2a assessment?

Cynical me is thinking this is because "Hearing-In-Noise" is a more marketable aspect of the medicine. It's harder to promote "hearing words in silence improved".

But I hope your assumptions are correct!

 

[Diesel]

Cynical me is thinking this is because "Hearing-In-Noise is a more marketable aspect of the medicine. It's harder to promote "hearing words in silence improved".

But I hope your assumptions are correct!

Agree that it might be. Up until recently, their marketing had focused on word recognition; a function of the standard word score. As a regulated company, marketing communications need to be backed with evidence. Maybe a p-value of 0.2 is enough from the Phase 1/2 to be confident in marketing a benefit?

 

[Philip83]

Agree that it might be. Up until recently, their marketing had focused on word recognition; a function of the standard word score. As a regulated company, marketing communications need to be backed with evidence. Maybe a p-value of 0.2 is enough from the Phase 1/2 to be confident in marketing a benefit?

Ah yes, you're right, "word recognition" is also a good term of course. But yeah, let's hope they're seeing improved results that are making them confident!

 

[Diesel]

Possibly there are a lot more hearing in noise patients who have damaged IHCs rather than just synaptopathy than it seems (and neither would show up on an audiogram).

Remind me again the link between IHC loss and hearing in noise deficits?

 

[FGG]

Remind me again the link between IHC loss and hearing in noise deficits?

The synapses in synaptopathy are between the IHC and the spiral ganglion. You can lose these connections without damaging hair cells (i.e. classic "cochlear synaptopathy") or if the IHC is destroyed itself then obviously there would be no IHC to synapse to.

In the JP Morgan talk, Frequency Therapeutics had said they could treat cochlear synaptopathy of the latter type because a newly regrown hair cell forms new connections.

 

[FGG]

Hmm...just found this:

Valproic acid promotes the neuronal differentiation of spiral ganglion neural stem cells with robust axonal growth

It seems Valporic acid may help with Spiral Ganglion neurite outgrowth, which presumably could mean help with synaptopathy in intact hair cells, too (presumably the new neurites would synapse).

It's possible they are finding out this is an effect of their drug too? They haven't explicitly said that, so it could be drawing too much of a conclusion but would be interesting.

 

[tommyd87]

So if and when FX-322 is released, will I have to go through an ENT? Or could I just contact the drug company that they have the right to distribute with and ask them to sort if out for me, or at the very least, steer me in the right direction?

Very worried about consulting the wrong ENT, as the ones I've seen here in Australia don't seem to be interested in new and upcoming treatments at all, or informed either.

Go to an ear specialist or ENT hospital.

I have happened to be aware that they tend to know what to do when it comes to this sort of stuff. I shall suggest that there will be ENTs and more specifically Otologists who will work with this treatment type. The problem with ENTs is that many of them are also working with what were accepted practices 30 or so years ago and you can actually find this out when you go get a second opinion on something and then get told by someone who is more up to date on things that what they are doing is no longer best practice and wrong.

When you have ENTs who try to tell you that there is no link between the ears and the nose, then you know there is a problem with what they do.

 

[tommyd87]

Possibly there are a lot more hearing in noise patients who have damaged IHCs rather than just synaptopathy than it seems (and neither would show up on an audiogram).

I reckon that if it is the case that you improve the volume of hearing at the speech frequencies for example, you are likely to be able to hear things a lot more loudly. Hence how you can hear better in noise.

 

[DebInAustralia]

So if and when FX-322 is released, will I have to go through an ENT? Or could I just contact the drug company that they have the right to distribute with and ask them to sort if out for me, or at the very least, steer me in the right direction?

Very worried about consulting the wrong ENT, as the ones I've seen here in Australia don't seem to be interested in new and upcoming treatments at all, or informed either.

Weren't the safety trials conducted at the Victorian Eye and Ear Hospital in Melbourne?

I'd present there or an otologist who has expertise in IT injections.

 

[Lucifer]

Weren't the safety trials conducted at the Victorian Eye and Ear Hospital in Melbourne?

I'd present there or an otologist who has expertise in IT injections.

That's true, the cochlear implant patients. Those ENTs there should know how to do the IT injection.

 

[Jack V]

Agree with all of this but I would add that I think it's a good idea to be an established patient at a practice/doctor already used to intratympanic injections rather than rely on those who would get brief training with the release of a popular new intratympanic drugs because you would greatly minimizes the risk of ear drum complications.

If you already have a doctor like this, you would be waiting less time vs being a new patient.

Doctors who routinely and regularly give IT injections are: ENTs who treat a lot of Meniere's patients or all Otologists (these are ENT subspecialists for the unfamiliar).

Great point.

When I was looking into intratympanic injections myself (I had a series of 4), I did a bit of research and got the impression complications among ENTs who regularly perform them are remote. Makes sense -
Generally, with medical procedures, a doctor who regularly does a thing tends to be good at it. Actually, that's probably true with anything.

So for sure, establishing a relationship with an ENT who's experienced giving injections, rather than one who's jumping on a bandwagon (should a bandwagon hopefully arrive), makes a lot of sense.

 

[serendipity1996]

Hmm...just found this:

Valproic acid promotes the neuronal differentiation of spiral ganglion neural stem cells with robust axonal growth

It seems Valporic acid may help with Spiral Ganglion neurite outgrowth, which presumably could mean help with synaptopathy in intact hair cells, too (presumably the new neurites would synapse).

It's possible they are finding out this is an effect of their drug too? They haven't explicitly said that, so it could be drawing too much of a conclusion but would be interesting.

Interesting find - when Carl LeBel was on the Tinnitus Talk Podcast he made an interesting comment when discussing cochlear synaptopathy. He was talking about the process of FX-322 working:

"It wouldn't be the first drug if it gets approved, where one didn't fully understand the mechanism of action." (on page 12 of the transcript).

I'm probably just reading too much into this but it's a slightly ambiguous comment and I wonder if it possibly suggests that the drug could also stimulate synapse growth?

I'm not sure though since both LeBel and Christoper Loose have emphatically stated in previous investor presentations, for instance, that it's only a synaptopathy drug where you have hair cell loss.

 

[frpp]

The FX-322 ClinicalTrials.gov page has the list of clinics that participated in the trial, and when Phase 3 comes around it should get updated/expanded. That could be a good place to start looking for doctors. Now's the time to build relationships with the right doctors because once FX-322 gets released it's going to be a crap show and a scramble, and I for one am not waiting to get it when it comes available.

 

[tiredofit]

That's true, the cochlear implant patients. Those ENTs there should know how to do the IT injection.

Can CI patients get FX-322 too?

 

[Lucifer]

Can CI patients get FX-322 too?

No. This was just to test the safety of the drug.

 

[Princebeyel]

Can CI patients get FX-322 too?

That was also a question of mine as I can barely wait for FX-322. My word recognition scores are so poor my life is depressing. However, I did go to the University of Miami and spoke to a CI doctor who said that they would cure hearing loss in my lifetime which was promising. He then continued to try to convince me that CI patients would be the first to get the medicine which to me sounded like bologna.

 

[frpp]

That was also a question of mine as I can barely wait for FX-322. My word recognition scores are so poor my life is depressing. However, I did go to the University of Miami and spoke to a CI doctor who said that they would cure hearing loss in my lifetime which was promising. He then continued to try to convince me that CI patients would be the first to get the medicine which to me sounded like bologna.

I admire that doctor's optimism on the future of eliminating hearing loss (the medical field could use more of that) but he seems not the least bit educated on FX-322.

I agree that what he said was pure bologna, not a smart move on his part telling a patient that.

 

[tiredofit]

That was also a question of mine as I can barely wait for FX-322. My word recognition scores are so poor my life is depressing. However, I did go to the University of Miami and spoke to a CI doctor who said that they would cure hearing loss in my lifetime which was promising. He then continued to try to convince me that CI patients would be the first to get the medicine which to me sounded like bologna.

Cochlear implants seem to help MOST recipients with tinnitus and hyperacusis from what I've garnered though. I asked around because I myself am pretty hard of hearing but not enough to be a candidate unfortunately.

 

[Gb3]

The FX-322 ClinicalTrials.gov page has the list of clinics that participated in the trial, and when Phase 3 comes around it should get updated/expanded. That could be a good place to start looking for doctors. Now's the time to build relationships with the right doctors because once FX-322 gets released it's going to be a crap show and a scramble, and I for one am not waiting to get it when it comes available.

I'm sure any reputable hospital will have access to FX-322.

You guys are really getting out of hand with these assumptions.

 

[Lucifer]

I admire that doctor's optimism on the future of eliminating hearing loss (the medical field could use more of that) but he seems not the least bit educated on FX-322.

I agree that what he said was pure bologna, not a smart move on his part telling a patient that.

Especially the part that cochlear implant patients can get FX-322 is not true at all.

 

[Princebeyel]

Cochlear implants seem to help MOST recipients with tinnitus and hyperacusis from what I've garnered though. I asked around because I myself am pretty hard of hearing but not enough to be a candidate unfortunately.

You mean fortunately! Lol I wish I could hear better and understand better what I hear.

 

[frpp]

I'm sure any reputable hospital will have access to FX-322.

You guys are really getting out of hand with these assumptions.

I agree. No doubt that it will be available in many reputable hospitals eventually, but the list of good doctors experienced with performing intratympanic injections and/or those who will at least be early adopters of prescribing FX-322 will be slim at first, and after already waiting so long I think most of us would like to have the procedure done as quickly and safely as possible. Personally I don't want to wait 6 months to god knows how long after this drug comes out to get the right ENT appointments. When FX-322 comes out I want it ASAP and if I can make preparations in advance to make that happen it's worth it to me.

 

[Princebeyel]

Especially the part that cochlear implant patients can get FX-322 is not true at all.

He said something along the lines because we had the pathway or some BS. My mom was convinced but when I asked him about FX-322 he had no idea what I was talking about.

 

[100Hz]

Cochlear implants seem to help MOST recipients with tinnitus and hyperacusis from what I've garnered though. I asked around because I myself am pretty hard of hearing but not enough to be a candidate unfortunately.

I have been thinking about this as well. Maybe cochlear implants stop the natural way ATP gets produced and leaked in a damaged cochlea that doesn't have an implant, that could mean there is no longer any ATP to interfere with nociceptors as it just becomes an artificial device directly stimulating the auditory nerve.

Do you retain any natural hearing function that runs alongside an implant or is it now purely the implant acting as the ear? I believe it wipes out what's left.

 

[FGG]

I have been thinking about this as well. Maybe cochlear implants stop the natural way ATP gets produced and leaked in a damaged cochlea that doesn't have an implant, that could mean there is no longer any ATP to interfere with nociceptors as it just becomes an artificial device directly stimulating the auditory nerve.

Do you retain any natural hearing function that runs alongside an implant or is it now purely the implant acting as the ear? I believe it wipes out what's left.

I think they meant loudness hyperacusis. I haven't heard of CIs helping noxacusis but that would be interesting if they did.

Is there such a study?

 

[Lucifer]

I have been thinking about this as well. Maybe cochlear implants stop the natural way ATP gets produced and leaked in a damaged cochlea that doesn't have an implant, that could mean there is no longer any ATP to interfere with nociceptors as it just becomes an artificial device directly stimulating the auditory nerve.

Do you retain any natural hearing function that runs alongside an implant or is it now purely the implant acting as the ear? I believe it wipes out what's left.

That's why I believe that FX-322 should stop ATP from leaking and stop pain hyperacusis. I would never go the CI route if I knew I will be cured with FX-322 in 2-3 years time and retain my normal ears.

 

[Lucifer]

I think they meant loudness hyperacusis. I haven't heard of CIs helping noxacusis but that would be interesting if they did.

Is there such a study?

@Orions Pain did share that cochlear implants helped a patient's pain so I'm assuming she was referring to pain hyperacusis.

 

[100Hz]

I think they meant loudness hyperacusis. I haven't heard of CIs helping noxacusis but that would be interesting if they did.

Is there such a study?

No study but there was a story recently on Facebook about a guy who'd established that his middle range frequencies were damaged and after he'd had a cochlear implant it managed to balance everything up and that by filling in the missing middle range gap with the cochlear implant it appeared to address the hearing imbalance and fix the hyperacusis. I'm not sure if loudness or pain hyperacusis was his main complaint but he said it definitely helped with the pain.

Here's another one from a while back:

https://blog.medel.com/cochlear-implants-for-tinnitus-hyperacusis/

 

[FGG]

No study but there was a story recently on Facebook about a guy who'd established that his middle range frequencies were damaged and after he'd had a cochlear implant it managed to balance everything up and that by filling in the missing middle range gap with the cochlear implant it appeared to address the hearing imbalance and fix the hyperacusis. I'm not sure if loudness or pain hyperacusis was his main complaint but he said it definitely helped with the pain.

Here's another one from a while back:

https://blog.medel.com/cochlear-implants-for-tinnitus-hyperacusis/

Oh ok.

I took @Orions Pain's anecdote as a loudness one (which is definitely uncomfortable and unpleasant but absolutely not in the way noxacusis is) and it seems that this is similar. Once again, I wish there was a standard terminology because it gets very confusing.