Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

No changes observed in the EHF audiogram, which was the thing I was still holding out for - either in Phase 2 or new Phase 1 study. This tells me the delivery issue argument no longer holds.

I think we have to accept that, for whatever reason we don't understand, this drug just doesn't work in humans in vivo.

I'm soul destroyed. No idea where we go from here. This is as good as over.

I truly am at a loss why that would be the case. It worked in hundreds of explanted cochleas. Can it just not get beyond the middle ear?

 

[spacehunter]

No changes observed in the EHF audiogram, which was the thing I was still holding out for - either in Phase 2 or new Phase 1 study. This tells me the delivery issue argument no longer holds.

I think we have to accept that, for whatever reason we don't understand, this drug just doesn't work in humans in vivo.

I'm soul destroyed. No idea where we go from here. This is as good as over.

I agree with you - besides the two days when I woke up with sudden deafness in my ear, this is the worst day of my life. 2021 did start so well with potential readout for OTO-413, hopefully good news for their drug against Meniere's and the readout for Phase 2a of FX-322. Now Otonomys Meniere's drug failed, they have to redo phase 1 for OTO-413 in 2022 and to make matters even worse the Phase 2 results of FX-322 are worse than our worst expectations.

I really hoped that the worst case would have been improvements in EHF audiograms and word recognition without benefits in normal hearing range...

 

[Kleiner]

So, the Phase 1b trial didn't succeed either?

 

[r34d1ng]

No changes observed in the EHF audiogram, which was the thing I was still holding out for - either in Phase 2 or new Phase 1 study. This tells me the delivery issue argument no longer holds.

I think we have to accept that, for whatever reason we don't understand, this drug just doesn't work in humans in vivo.

I'm soul destroyed. No idea where we go from here. This is as good as over.

Dude, if results are biased as they say, they are literally useless. They don't prove absolutely nothing, neither that the drug works nor that it doesn't. Biased results = discarded results.

 

[Aaron91]

I truly am at a loss why that would be the case. It worked in hundreds of explanted cochleas. Can it just not get beyond the middle ear?

Not possible. We have the perilymph samples from the cochlea implant study.

 

[Keith Handy]

Quick thought: it would be tricky to fake a bad word score to get in. You would have to hear the word, recognize it, then quickly think of a word that it sounds similar to, without a suspicious/noticeable pause. The bluffing would be kind of obvious, in my opinion, unless you were a skilled improvisor.

 

[Aaron91]

Dude, if results are biased as they say, they are literally useless. They don't prove absolutely nothing, neither that the drug works nor that it doesn't. Biased results = discarded results.

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

This drug is dead. It doesn't work in humans, period.

 

[FGG]

Quick thought: it would be tricky to fake a bad word score to get in. You would have to hear the word, recognize it, then quickly think of a word that it sounds similar to, without a suspicious/noticeable pause. The bluffing would be kind of obvious, in my opinion, unless you were a skilled improvisor.

They just mark whether you got the word right or not. Audiologists aren't used to people faking that.

 

[RichieTheKid]

That's apparently not the problem they encountered. Apparently, the placebo group also improved word scores and their audiologist consultant said flat out it's because he believes many people faked worse word scores to get in the trial.

That sucks.

 

[Dizzyhead888]

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

This drug is dead. It doesn't work in humans, period.

Yes, this confused me.

Can anyone confirm?

There is a huge difference between "improvements were not discernible over placebo" vs. "there were no improvements in either group at all".

 

[Piet]

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

This drug is dead. It doesn't work in humans, period.

I don't know why you are being so negative about it. FX-322 still works but just doesn't have additional benefits to multi dosing. They also don't have all the data yet so it's a bit too early to draw conclusions.

 

[FGG]

Yes, this confused me.

Can anyone confirm?

There is a huge difference between "improvements were not discernible over placebo" vs. "there were no improvements in either group at all".

That would be very different.

I imagine people could make their EHF audiogram seem worse too. I.e. people who would have no problem faking a word score could easily click the button later if they thought it would help them get in the trial...

 

[r34d1ng]

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

This drug is dead. It doesn't work in humans, period.

That is no how statistics work. Biased data produce biased results. You can't just simply pick unbiased results from biased data because every single thing is biased in one way or the other.

 

[Jack Straw]

They stated in the webinar; no observed changes in tinnitus from baseline in Phase 2a, although they only had data from one patient for some reason, as I understood it.

The really bad part though that came up was that there were no improvement in the high frequency range in the single dose Phase 1b study. This sucks really bad imo.

One patient is not enough to make any claim regarding the effectiveness of this drug on tinnitus.

Also, aren't the higher frequencies deeper inside the cochlea, which they are currently having issues getting the drug to?

 

[Diesel]

How do we explain the long-term durability scores from the Phase 1/2? What happened then?

 

[Aaron91]

I don't know why you are being so negative about it. FX-322 still works but just doesn't have additional benefits to multi dosing. They also don't have all the data yet so it's a bit too early to draw conclusions.

I'm not being negative. I'm reading between the lines. They clearly said there were no EHF improvements in the single dose follow up Phase 1 study. This has nothing to do with multiple dosing or placebo or artificially deflated WR scores. None of that explains why there was no absolute improvement (let alone discernible improvement) in the EHF range where we KNOW the drug is concentrated.

I don't want to break anyone's heart or resolve here but we also need to be realistic. This drug is dead.

 

[Jack Straw]

I imagine if people made their EHF audiogram seem worse too. I.e. people who would have no problem faking a word score could easily click the button later if they thought it would help them get in the trial...

This is also why placebo increased too. This is just a shitshow.

 

[r34d1ng]

Yes, this confused me.

Can anyone confirm?

There is a huge difference between "improvements were not discernible over placebo" vs. "there were no improvements in either group at all".

"improvements were not discernible over placebo" = "there were no statistically significant improvements in either group at all"

 

[FGG]

I'm not being negative. I'm reading between the lines. They clearly said there were no EHF improvements in the single dose follow up Phase 1 study. This has nothing to do with multiple dosing or placebo or artificially deflated WR scores. None of that explains why there was no absolute improvement (let alone discernible improvement) in the EHF range where we KNOW the drug is concentrated.

I don't want to break anyone's heart or resolve here but we also need to be realistic. This drug is dead.

Did they say no absolute improvements or no statistically significant improvements over placebo? Two very different things.

Because we now know people faked results to get into the trial, which could include EHF since it is not standard and was likely done for many during recruiting.

 

[Ilias T]

The results are not failed, just unexpected. It looks like they plan to stay on single dose.

They need to be more careful with participants next time. Every study and trial is a step closer.

 

[100Hz]

The Phase 2a study seems null and void because of bias, fair enough, but what's the deal with the Phase 1b study because on the one hand it looks like early results for a third of patients showed 10% or greater improvement in WR, but on the other hand also apparently showed no changes in EHF.

I'd still have some confidence if it wasn't for this.

 

[Zugzug]

I wish there was detailed data. It would be so much easier to analyze this faking business.

 

[Aaron91]

"improvements were not discernible over placebo" = "there were no statistically significant improvements in either group at all"

In respect of EHF, go to 36:40 of webcast:

https://edge.media-server.com/mmc/p/gheyi6hn

Carl says: "no real changes from baseline and no changes between the groups". In other words, no absolute improvements in either group and no statistical significance either. I agree that statistical significance isn't necessarily meaningful if we see both groups improve their EHF over baseline, but neither group improved their baseline at all, even though we know the drug is concentrated in the EHF range.

The only other possibility is that somehow the gains were between 16 kHz and 20 kHz which they didn't test for, but somehow I really doubt that.

 

[Piney]

Like I said, why isn't there more hype on OTO-313 tinnitus results? At least they posted something positive even if it's in early stages. I'll be following that thread for the upcoming trial info.

 

[Piney]

The trial can be faked if you memorize the words from the first batch to the second and they're the same. I couldn't tell you though if they were the same since I couldn't decipher.

 

[Nobody19]

This is disappointing. I'll read all of your posts after work.

 

[100Hz]

My ears were too sensitive to listen. Was it "no changes" or "no changes vs placebo"?

I was having trouble with a lot of it myself. I actually missed that bit in the presentation but it's been mentioned above in the thread a couple of times.

The really bad part though that came up was that there were no improvement in the high frequency range in the single dose Phase 1b study. This sucks really bad imo.

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

 

[paul mclean]

So I bet you they found this out by people who didn't have that bad of hearing anyway that faked their WR scores to moderate/bad and then they believed they got FX-322 from placebo when they really didn't so then they did the WR tests normally without faking anything. Therefore the trial examiners would have noticed the difference.

It's irritating but I don't think this is that bad.

They can still increase the dosage. We don't know if their doses are modest still.

It could work better with 2 week breaks instead of a week.

What I'm worried about is if they have to do another Phase 2 trial and then a Phase 3. If that's the case I'll be extremely fucking pissed off.

The drug works. Dosage and delivery need to be worked on.

I read somewhere that drug delivery might move towards using a specific dye that is used to identify osteoporosis and the dye can make drugs stay at their intended locations for a long time. Apparently used with biosphosphonates.

Anyway now to wait another 2 months to see the final verdict. Hopefully the FDA is reasonable as Frequency Therapeutics obviously have many trials going for the one drug...

Don't beat yourselves up too much people.

 

[dd314]

If I heard correctly, they didn't say the improvements were not discernible over placebo with regards to EHF. They said there were no improvements in either group at all.

This drug is dead. It doesn't work in humans, period.

Why did it work in Phase 1/2?

 

[Aaron91]

Like I said, why isn't there more hype on OTO-313 tinnitus results? At least they posted something positive even if it's in early stages. I'll be following that thread for the upcoming trial info.

They use a different set of words in each test.