Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Now that I understand the issue, there are varying levels of theorizing. Obviously, the big question is "how many cheaters were in the study?"

Then, once you have X cheaters, how were they distributed (drug vs placebo)? Then, how did the individual cheaters happen to behave? Just as a strawman, if the cheaters that landed in the placebo maintained their cheating with low baselines, they will have artificial inflations after treatment. If the cheaters that performed normally at baseline landed in the drug group, they would have a ceiling effect.

Obviously, that's a super bullish way to look at what happened. In my opinion, the most likely situation is that there were a few cheaters, they put very little thought into it, just faked low screens and baselines. At least some landed in the placebo group. Maybe a proportionate number landed in the drug group.

It's very possible that FX-322 is still largely ineffective, with the exception of helping word scores in some super responders.

It depends on why the word scores increased. Not just the super responders responded in Phase 1. What exactly was affected? If it is say IHCs first (for instance), the drug is more effective than it looks. Something is happening if it's not OHCs...

 

[rei]

It's extremely hard to be reasonable and care about the science and the bigger picture when you're desperate. It wouldn't surprise me if it was a large number of people who lied.

Do many people sign up as guinea pigs for any type of experimental drug strictly for science, without some great hope of receiving the treatment?

 

[Tezcatlipoca]

It's very easy to fake a word score, all you have to do is say I don't understand. I think it's harder to fake an audiogram.

And that's without taking into account how often audiologists fuck up.

 

[Gb3]

And that's without taking into account how often audiologists fuck up.

I don't know why audiologists are the enemy here.

 

[Lucifer]

Do Frequency Therapeutics know if the audiologists fucked up as they were worried about losing their jobs? They really need to use in-house people.

 

[Drachen]

It's extremely hard to be reasonable and care about the science and the bigger picture when you're desperate. It wouldn't surprise me if it was a large number of people who lied.

I agree. As shitty a thing it is to do, it's also pretty shitty to have to live with such debilitating conditions. The responsibility is really on the biotech like Frequency Therapeutics to ensure they can properly detect and screen out possible fakers (or exaggerators).

 

[Gb3]

Do Frequency Therapeutics know if the audiologists fucked up as they were worried about losing their jobs? They really need to use in-house people.

Even if FX-322 succeeds, we are still going to need audiologists to diagnose people, and FX-322 doesn't treat all types of hearing loss

 

[Gb3]

I agree. As shitty a thing it is to do, it's also pretty shitty to have to live with such debilitating conditions. The responsibility is really on the biotech like Frequency Therapeutics to ensure they can properly detect and screen out possible fakers (or exaggerators).

I disagree. It's about seeing the big picture and being a good human.

 

[FGG]

I don't know why audiologists are the enemy here.

Especially considering these were at testing sites involved in multiple trials, I don't buy any "audiologists being paid by hearing aid companies to mess up the trial" conspiracies.

 

[asey20]

I don't know why everyone is speculating this and that and blah blah blah. Maybe just let them find out why the results were like that??? Stop blaming audiologists and even people for being fakers. Word recognition score isn't even fool proof test. It's easy to hear two words that sound similar and just happen to guess the right one.

Besides, hindsight is 20/20 and I can say that the way they designed the Phase 2 study looked great IF it had worked as they and we were expecting it to. However it didn't and there is a lot that needs to be taken into consideration moving forward.

Why did Phase 1 results work so much better than the Phase 2? This is an important question that they have to figure out moving forward.

Btw, the FREQ stock prices are sitting low. Not sure if this is as good a time as ever to buy this stock? It would be better if they had more in their pipeline but it seems like that's probably the reason why it tanked so much.

If anyone could tell me why they think it is or isn't a good idea to invest in FREQ at this point, then I'm all ears.

 

[FGG]

@FGG, for severe hearing loss sufferers, what would be considered a successful trial? Would that be if the improvement in their word scores using one dose of FX-322 is 10% more from their baseline? Would restoring high-mid frequencies for severe hearing loss sufferers do anything to improve their word scores?

A successful trial would mean significant word score increases over placebo. Without knowing why people in Phase 1 especially improved, no one could tell you what or where we would see this in that case.

 

[Tezcatlipoca]

A successful trial would mean significant word score increases over placebo. Without knowing why people in Phase 1, especially improved, no one could tell you what or where we would see this in that case.

There have been those improvements in a couple of trials now, could they move forward and get the drug out just with those results, whitout being able to explain them?

 

[FGG]

There have been those improvements in a couple of trials now, could they move forward and get the drug out just with those results, whitout being able to explain them?

No. You have to explain your results. Unless I'm confused by what you mean.

 

[Tezcatlipoca]

No. You have to explain your results. Unless I'm confused by what you mean.

No, you got it right, I asked because I believed you could move forward without explaining those results, as long as they were positive results of course.

 

[FGG]

I don't know why everyone is speculating this and that and blah blah blah. Maybe just let them find out why the results were like that??? Stop blaming audiologists and even people for being fakers. Word recognition score isn't even fool proof test. It's easy to hear two words that sound similar and just happen to guess the right one.

Besides, hindsight is 20/20 and I can say that the way they designed the Phase 2 study looked great IF it had worked as they and we were expecting it to. However it didn't and there is a lot that needs to be taken into consideration moving forward.

Why did Phase 1 results work so much better than the Phase 2? This is an important question that they have to figure out moving forward.

Btw, the FREQ stock prices are sitting low. Not sure if this is as good a time as ever to buy this stock? It would be better if they had more in their pipeline but it seems like that's probably the reason why it tanked so much.

If anyone could tell me why they think it is or isn't a good idea to invest in FREQ at this point, then I'm all ears.

It's not like people here came up with the Phase 2a fakers idea, that's what Frequency Therapeutics said when they mentioned "inconsistency" with baseline and records.

As far as stock, we are at best looking at a delay and possibly a Phase 2 restart. The market wouldn't love that imo. Though part of it also depends on how you feel about their MS drug as they are looking to file an IND later this year.

 

[Lucifer]

If the worst case scenario happens and the severe hearing loss clinical trial shows minimal or no improvements due to drug delivery, then the FDA should allow FX-322 to go through the pivotal phase early next year with the mild-moderate hearing loss indication, using FX-322's current delivery method.

If it helps tinnitus as well, this would be a bonus and could convince the FDA more easily to allow FX-322 to do a pivotal phase early next year as a lot of people in the military suffer from tinnitus due to the 3M earplug fuck up. Even one dose of FX-322 could change someone's life.

 

[FGG]

If the worst case scenario happens and the severe hearing loss clinical trial shows minimal or no improvements due to drug delivery, then the FDA should allow FX-322 to go through the pivotal phase early next year with the mild-moderate hearing loss indication, using FX-322's current delivery method.

If it helps tinnitus as well, this would be a bonus and could convince the FDA more easily to allow FX-322 to do a pivotal phase early next year as a lot of people in the military suffer from tinnitus due to the 3M earplug fuck up. Even one dose of FX-322 could change someone's life.

If the results of Phase 2a are suspect and there is no change in the severe cohort, Frequency Therapeutics would have to figure out the discrepancy between Phase 1 and the new results. No question. If they made a convincing enough case by combing over data and looking at the ones that did respond, then I think they could restart Phase 2 with an entirely new trial design.

I don't see a path forward directly to pivotal (Phase 2b/3) without some great results from the other arms. Even then, it's a bit questionable that it could happen without a serious delay because they would have to, in my opinion, figure out the actual reason for dramatic word score gains without corresponding audiogram findings (unless we happen to see them in the severe arm). If there is a hearing effect and it is not due to OHC regrowth detected on audiogram (with one injection at least), it would be foolish to design a pivotal trial without figuring that out.

Just my opinion.

 

[Sunshine007]

I'm new here and totally enjoy the quality discussion...

The notion that the fakers somehow had a significant effect on the result has the following arguments going against it:
1) Depressed starting scores in the treatment arm (fakers) probably increases the effect size;
2) Frequency Therapeutics says the improvement in the treatment arm was damped and lower than observed earlier.

I'm wondering if the multiple injections can be the significant factor here. I'm not saying fakers were not there, just that it cannot be the dominant part of what was reported on phase 2A.

Assuming everyone damped their starting scores to varying degrees, not sure how you would fake to be exactly around the range FREQ wanted it to be. But even if they did, we might have seen increased effect size compared to phase 1 in the treatment but perhaps not statistically significant due to placebo improvement.

 

[Lucifer]

If the results of Phase 2a are suspect and there is no change in the severe cohort, Frequency Therapeutics would have to figure out the discrepancy between Phase 1 and the new results. No question. If they made a convincing enough case by combing over data and looking at the ones that did respond, then I think they could restart Phase 2 with an entirely new trial design.

I don't see a path forward directly to pivotal (Phase 2b/3) without some great results from the other arms. Even then, it's a bit questionable that it could happen without a serious delay because they would have to, in my opinion, figure out the actual reason for dramatic word score gains without corresponding audiogram findings (unless we happen to see them in the severe arm). If there is a hearing effect and it is not due to OHC regrowth detected on audiogram (with one injection at least), it would be foolish to design a pivotal trial without figuring that out.

Just my opinion.

Ok, praying that both age-related and specifically severe hearing loss trials show meaningful word score improvements. If the severe hearing loss trial shows meaningful word score improvements this will be the best chance at going to the pivotal phase early next year.

 

[Street Novelist]

To be waiting this long, only to have it be a massive disappointment, I don't know what to say. I'm afraid of the people who were already on the edge before the results came out. I hope no one commits suicide or does anything regretful. Frequency Therapeutics really needs to get this figured out fast and not have us wait several more years.

 

[Bill Bauer]

No problem. It's 5 am right now so I'm about to go to bed but if I recall correctly, Neuromod's Lenire and Minnesota's respective devices are very dissimilar. Early on there was some hope that Lim's promising research in signal timings could optimize Neuromod's (Ireland) approach, but that didn't come to fruition. Honestly can't remember how Minnesota's device distinguished itself from Shore's, but I remember the two US devices having more commonalities than Neuromod's. Neuromod stimulates the tongue (vagus nerve?) while Shore's stimulated nerves in the neck/jaw.

Can't remember much from Minnesota because it's unfortunately irrelevant now.

I guess our best hope now is Susan Shore's device. Are we expecting anything from them in the next five years?

 

[Tezcatlipoca]

I don't see a path forward directly to pivotal (Phase 2b/3) without some great results from the other arms.

That's the weird thing imo, the language of the press release seems to imply they're going on ahead.

 

[Jazzer]

How many times have we been here before?

A drug, a treatment, shows nothing much more than a hint of promise and then there appears to be some kind of anticipatory euphoria, probably whipped up by those with much to gain from an investment programme, and people start to throw their hard earned money at it.

My suggestion would be to let the doctors, scientists, big pharma get on with doing their job, while us sufferers explore more deeply what is available to us in the form of coping methods, deep relaxation, meditation, etc. without resorting to the psychologically damaging practice of 'cliff-hanging,' and the subsequent disappointment and despair that inevitably follows.

It is a sobering thought that in 200,000 years of human habitation on this planet, (some evangelical groups reduce that down to a mere 10,000 years of course), no agency has ever come up with anything to reduce the noise level of tinnitus by as much as one solitary decibel.

Time to just cool it, relax, meditate etc... in my humble opinion.
To put it in some context, I have suffered, and I do mean 'suffered' for over 30 years of my life.

Dave x
Jazzer
(the video man)

 

[knickfan]

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

As I mentioned — I got the drug in the first trial and the placebo in the second. They do not tell you what dose you received (there were 3 levels).

SPI-1005 was definitely helpful. I think it will help a a lot of you once its approved. It is just insane how long the process takes. I was in Phase 1 almost 4 years ago and this drug is still 4/5 years from being approved.

It is not a one-time miracle pill. I was so far long with my Menière's journey by the time I took it. There was already soooo much damage done to my ear. I think this drug will be so helpful to people, especially earlier on in their journey.

I guess the best way to sum it up is: SPI-1005 does a great job of lowering the inflammation in the inner ear. It basically does what we all wish steroids would do. I took over 15 shots of steroids in my ear and they did nothing. This pill is able to break the blood brain barrier and puts out some of the fire. For some of you it may completely put it out. I think it is something you can you use when your ear flares up. I definitely felt it working. I also knew in phase 2 I got the placebo. There was a big difference.

Wish you all the best — Keep your heads up!!

They will figure it out. Hell... they got us a vaccine in 9 months. It will happen!!

 

[Bill Arsenault]

I don't know why audiologists are the enemy here.

I imagine it's just the thought of a glorified hearing aid salesman possibly ever having anything to do with pivotal trials for a hearing loss cure; combined with some of our experiences dealing with their attitude towards tinnitus.

 

[RichieTheKid]

Ok, praying that both age-related and specifically severe hearing loss trials show meaningful word score improvements. If the severe hearing loss trial shows meaningful word score improvements this will be the best chance at going to the pivotal phase early next year.

Listen man, where are you located? Even if FX-322 doesn't work amazingly right now, there's still some proof it has beneficial effects. Who knows, it may even work over time as some people who took it noticed. I'm going to try and get it somehow, I don't know how and when - I'm hoping there's a trial in the UK later this year, but I view it as a way to get by on an improved level until technologies advance and even better stuff comes out.

 

[Pero1234]

Can someone help me better understand the Phase 1b open label study?

If I understand correctly, FREQ treated only one ear with a single dose of FX-322. Then 35% of test subjects saw an increase of 10% or more in word scores in the treated ear?

Now, did they treat the other ear with a placebo? Or did the other ear not receive any injections?

I fear that, if the other ear did not receive a placebo, that there might be a bias problem here as well.

I know that when people want something to work the subconsciously try harder to recognize words.

In this case, if someone would know which ear got treated... I would not be surprised that the results were 10% better. Even if FX-322 did not work.

Unless of course the other ear received a placebo. In that case the increased word scores would be solely linked to FX-322. That would restore my faith in FX-322.

 

[FGG]

I'm new here and totally enjoy the quality discussion...

The notion that the fakers somehow had a significant effect on the result has the following arguments going against it:
1) Depressed starting scores in the treatment arm (fakers) probably increases the effect size;
2) Frequency Therapeutics says the improvement in the treatment arm was damped and lower than observed earlier.

I'm wondering if the multiple injections can be the significant factor here. I'm not saying fakers were not there, just that it cannot be the dominant part of what was reported on phase 2A.

Assuming everyone damped their starting scores to varying degrees, not sure how you would fake to be exactly around the range FREQ wanted it to be. But even if they did, we might have seen increased effect size compared to phase 1 in the treatment but perhaps not statistically significant due to placebo improvement.

They were saying everyone increased their word scores significantly, including placebo so there was an increased effect in all groups but no difference from placebo (which doesn't differentiate the drug from placebo in the trial in that case). Their claim is that they found "inconsistencies" that point to it being related to people artificially depressing their word score to meet trial requirements.

 

[ThomasRobert]

Sorry, I was just recovering from grief and shock.

I wish someone could explain which of the ongoing studies has got the trial design fixed (without fakes and cheaters)?

Which of the studies got the trial design fixed:

FX-322-111
FX-322-202
FX-322-112
FX-322-113

Are they all with trial design flaws, and no proper, accurate hearing tests?

Another question, FX-322-111 study showed 10% improvement which is not an accurate and real improvement, so why are we hoping for better results from FX-322-202 & FX-322-112?

As a side note, I hold Frequency Therapeutics accountable for this pure gross negligence.

 

[FGG]

That's the weird thing imo, the language of the press release seems to imply they're going on ahead.

"Going ahead" does not necessarily mean straight to pivotal. All they said was "pivotal in the future." I would be surprised anyway because the Phase 2a data seems unusable unless they can parse out individual case by case and the FDA lets them do that. There would be no point requiring Phase 2 trials if it didn't matter if results were muddied.