Frequency Therapeutics — Hearing Loss Regeneration

Reaching the market is not the sole purpose of a clinical trial. Much to learn for them, no matter what happens.

It started with Genvec : for the first time in History, we are trying to regenerate the human inner ear. So we should keep in mind the big picture. It's only the beginning of all this.

 

Yes, I agree. Maybe it has something to do with the fact that Cochlear Limited, one of the three suppliers of cochlear implants to the US, is based in Australia and the trial will be performed on prospective adult CI recipients. A connection there somewhere.

 

Why should I look into decibal therapeutics? Are they aiming to treat tinnitus as well as hearing loss specifically?

look

 

Is this seriously a potentially viable solution to hearing loss (mine is noise induced)...if so then I'm excited and hopeful. Not only could it save my hearing it could ultimately save my life. Right now I am just existing

 

We could say that we have hearing loss if the drug works by the way we can take that madicine paying it. All depends if it is really effective or not. Keeps our experances high .

 

I'm quoting:

Primary outcome [2]
To assess the tolerability of intratympanic injection of FX-322. This is evaluated via treatment-emergent adverse events (TEAEs); physical examination; Visual Analog Scale for pain, Tinnitus Visual Analog Scale (TVAS) and the Tinnitus Handicap Index (THI): to assess potential to cause, exacerbate or ameliorate tinnitus, and Vertigo Symptom Scale (VSS) Questionnaire and Dizziness Handicap Index (DHI)

 

Right, they are evaluating those items in the context of the injection, not as actual study outcomes. We know that IT injections are generally well-tolerated so the only issue here is whether there would be something weird about FX-322 (hopefully not!). The reality is that they will learn next-to-nothing about TEAEs with 9 treated individuals. Moreover, they won't learn anything meaningful about fx-322 and tinnitus (or hearing) given that the subjects will undergo a CI operation making it impossible to know whether the drug helped or hurt anything.

They are really after two things: 1) how much fx-322 makes it into the inner ear (hopefully a lot) and 2) how much of it makes it into the bloodstream (hopefully none).

 

Yes they are! If FX does not work I would expect a cure to come from Decibel maybe 10-20 years who knows.

 

In 10 to 20 years I'll be dead and Decibel probably won't exist! Advances are made by learning from both failures and successes. I view research as an exponential, not linear, trajectory. I believe the path to be much shorter than 20 years.

 

@Aaron123
I wondered something about FX-322. I read the post that you have sent to inner ear headline.
And there was saying that FX-322 is for chronic noise induced hearing loss.
Doesn't this drug work for other types of loss like drug induced ?
(I have read this won't work for who has genetic loss)

 

Really good question. The lead indication, and what people from Frequency talk about, is noise induced hearing loss. So anything beyond that is speculation. That said, it makes sense that other causes of hair cell death that do not damage the supporting cells could be addressed by this approach. I haven't looked into hearing loss due to chemotherapy drugs or IV antibiotics enough to know the specific mechanism of hair cell loss, but if it does not damage the supporting cells I would think this approach would work.

 

I'm still not 100 percent sure what this means. I have lost my hearing much quicker than normal. It is due to genetic factors. I think usually this means someone that is born deaf due to a missing or defective gene. We still don't know why some people lose their hearing faster than others. I think it is all genetic.

the fact that the genvec trial did not work on Jeff from KS was disappointing as accelerated hearing loss due to genetic factors ran in his family.

If this is just for someone that loss his/her hearing due to a rock concert than I am in trouble. I'm sure some of my loss was due to noise induced hearing loss from rock concerts, but overall I blame some defective or missing gene. There are many people that naturally lose their hearing by age 60 and I'm sure genetics plays a role in that as well. So will this not work for them?

 

Yes, this is what David Lucchino meant by "genetic hearing loss" in the radio interview.

 

Probably shouldn't stray too far off the Frequency topic, but there is a spectrum of genetic issues. If there is a fundamental genetic defect in hair cells, then creating more hair cells with the same defect will not restore hearing. There are other genetic issues that do present later in life. I think it really depends on the specific type of defect. There's a lot of information here: https://www.ncbi.nlm.nih.gov/books/NBK1434/. Should probably start a new thread to talk about this in more depth.

 

I am only saying that because they doing a lot they want to help people with genetic conditions also protect the ears. They have a lot on the table. A guy on forum was saying 3 years for a growth factor like shimbo from South Korea I can only hope 3 years!

 

https://www.biocentury.com/biocentu...6-02/how-hearing-loss-became-investable-space

 

I have high hopes for Frequency Therapeutics. Coincidentally, I just finished reading a book called "The Gene" (https://www.amazon.com/Gene-Intimate-History-Siddhartha-Mukherjee/dp/1476733503) which is an amazing look at the history of the discovery and unmapping of the human genome.

What stood out to me was the relative rapid pace of the progress we have made as a species with regards to medical technology. This stuff was un-THINKABLE even just 50 years ago. I know that when one has T every day can be an exhausting battle, so the idea of waiting 3-5 years for some new treatment to come out seems like an eternity. But this is actually such a small slice of time on the larger scale of things that it's almost the blink of an eye as far as medicine goes. I am confident than one day the riddle of T will be unlocked, and moreover, that I will be around to see it. Depending on the risks involved and how much my T has bettered or worsened at that point will inform whether I decide to undergo treatment or not, but just the fact that this sort of thing will be possible in the not-too-distant future for millions of people puts a huge smile on my face.

 

Frequency 's Phase I trial is scheduled to launch in mid-2018.
https://www.lifescienceleader.com/doc/companies-to-watch-frequency-therapeutics-0001

 

Unfortunately I don't see this as news (unless there is something in the part of the article I can't see since I am not a subscriber). It is consistent with the interviews where folks from Frequency are saying "12 months" (down from 12 to 18 months from the beginning of the year) so it is likely a paraphrasing of that language. Hopefully we will get an official announcement or an entry into one of the trial registries soon. They seem to be on track though that impression largely comes from press releases - though I did post some evidence that they apparently restored hearing in mice prior to August 2016.

 

If there was no promise, I don't think Frequency would be able to attract heavy hitters like this. http://www.pmlive.com/pharma_appoin...ens_management_team_1192088?SQ_DESIGN_NAME=2& I'm very optimistic.

 

There is something I do not understand.
FT is planning this trial to determine how much of this FX322 ends up in the perilymph fluid (and blood plasma).
They want to do this with people that undergo cochlear implant surgery.

So they want to see how much of this FX322 permeates through the round window if I understand correct.
At timepoint 1 they want to take perilymph fluid (in surgery only). I see 1,2,4,6, 24h and 72h post injection.
Surely they can only test this perilymph fluid once, during surgery?
Or is it possible to test this perilymph fluid post surgery?
How else will they be able to assess how much of this FX322 gets inside the cochlea at different times?

 

They can only obtain perilymph fluid during surgery.

Timeline for primary outcome 1:

1) "Blood plasma is taken at baseline and screening"

2) Injection: "The participants will differ in obtaining Placebo (12-24 hours prior to implantation) or FX-322 (18mg) and the time window for the injection (either 12-24 hours prior to the surgery, 3-5 hours prior to surgery or 0.5-2 hours prior to the surgery). "

Since perilymph fluid is taken at surgery, they can look at concentrations of FX-322 in the fluid at 3 different time points (or more since there will be variability in the time of injection relative to surgery in the 9 patients).

3) Surgery: "Perilymph fluid is taken in surgery only."

4) Post-surgery: "Blood plasma is taken at ... 1,2,4,6, 24h and 72h post injection." No mention of perilymph fluid.

You can construct similar timelines for the other outcomes.

 

@Aaron123
Thanks. This makes sense to me.
Much appreciated.

 

When there is regeneration (what was witnessed in mice). How fast is this regeneration?
Days, weeks, months?
When mice are treated 24 hours after noise induced hearing loss and results are visible soon after, how soon is this?
When people that undergo CI surgery and get this FX-322 injected 24 hours prior to surgery, surely they will not miraculously notice improvement within this time frame already?
This idea is probably silly

 

As far as I can tell from the slide in the picture in the newspaper article, it was measured 30 days after injection. Obviously Frequency knows the answer to this, and presumably so will we when the next paper is published.

Based on the paper from February, they will not.

 

Who thinks this will work on humans? And do you think it will take off like laser eye surgery?

 

Restoring hearing loss, no doubt about it.

Tinnitus is an other story, just wait and see.

 

Personally, if my hearing were restored, it would mean less tinnitus, more external input to the brain equals less tinnitus in my situation. I can feel my brain going crazy looking for lost input (especially when I try to listen to exterior sounds and I can't hear them properly)

 

That is actually a pretty likely comparison. I keep thinking people will be lined up for a cure to hearing loss -- that the demand will be overwhelming. But maybe not. Not everyone with vision loss opts to have laser eye surgery; it's quite possible that not everyone with hearing loss would opt to get it corrected, especially if the loss is mild.

Of course, I still think the demand will be high from people with severe hearing loss like me.

 

Co-founder of frequency shares your point of view. More input = less tinniths. I hope it works too. More input should normalize things.