Frequency Therapeutics — Hearing Loss Regeneration

[Mathieulh]

Stick around for SPI-1005.

I haven't seen any of the initial trial outcomes for this drug. Is this even successful at all?

 

[Ed209]

In that case, it could be a misunderstanding. I thought by ever, he meant of the main people deep diving recently, which is true. We were doing all sorts of analysis and looking at the pharmacology graphs, the statistics, the preclinicals, etc. I don't think anyone who deep dived expected a miracle. I would even go as far as say that no changes for multiple doses was something people were prepared for.

I don't think most people expected this. If they did, they wouldn't have invested on their own free will.

I completely understand. There was a lot at stake.

 

[Aaron91]

Do you mean to say the bear thesis was born out of group data?

Pretty much. 4/15 responders on audiogram at 8 kHz isn't anything to write home about, neither is 6/15 responders on WR score.

 

[Pink Noise]

I feel really sad today:
Yesterday I was passed over for a promotion at work
Today this ... + lost $1.6k stock (first ever trade in my life)
T is no better still whistling over everything


I'm amazed at how Ive taken it all.

 

[dd314]

I haven't seen any of the initial trial outcomes for this drug. Is this even successful at all?

Yes, it lowered tinnitus in Meniere's patients.

 

[musicblue]

Big sense of Titanic today. This thread seemed unsinkable at one point. Tbh I am personally interested in the tinnitus side of things here and am wondering if there is any chance this drug had a beneficial effect in this area despite the other areas appearing negligible in benefit?

Do you think the team have even considered this area for reporting or are they for now just focused on the word/hearing outcomes? The report seems vacant in the tinnitus area.

 

[nocticolor]

 

[Pink Noise]

Maybe they added tinnitus to secondary outcomes to diversify the possibility for use?

 

[Zugzug]

Pretty much. 4/15 responders on audiogram at 8 kHz isn't anything to write home about, neither is 6/15 responders on WR score.

If we're doing play by play as a form of therapy, I'll add lol. I'm speaking for my own opinions only.

Obviously, I saw the 4/15 and 6/15 numbers. What I just couldn't shake, really at all, was the insane unlikelihood of seeing those huge WR responders. I still can't. Then there was the fact that the <= 90% word ceiling reduced the WR to 4/6. Of the 2/6 non-WR responders, 1 was close and the other wasn't, but they just happened to be the person in the group with the shortest duration. For the same criteria, the placebos looked exactly like placebo data: 2 insignificant improvements and 2 insignificant decreases.

Really, my bull thesis was three fold, and I almost worked under the assumption that I didn't care about multiple dosing.

1) Placebos cannot improve in WR to the level that we saw from a few people in Phase 1. I didn't consider that someone could start low from a bias to get in. Never crossed my mind.

2) Recruiters would be close enough to the hardcore responders that even though the data wouldn't be perfect, obvious group level improvements would occur. Conservatively, the results for 1x, 2x, 4x combined vs placebo would be plenty strong enough so that even if statistically significant stratification didn't occur, we would all take a deep breath and see amazing >= 1 dose results.

3) Even if we say the 4/15 >10 dB improvement at 8 kHz compared to 0/8 for placebo isn't statistically significant (it wasn't, but the p-value wasn't too bad), surely the EHF would make it based on the pharmacology study.

Really, I was the most wrong about 1) and 3) and we don't know about 2). What we do know about 2) is that even if they applied a filter and theoretically had a good, quadruple blinded process, there's just rough, unforeseen issues with study design.

I am shocked that all 3 of my thesis points were destroyed.

 

[asey20]

I saw that the hype was leading up to this unfortunately. I could see the whole dream collapsing with other companies like Otonomy, etc. having not achieved desirable results. IMO we are wasting time dreaming about these companies who have funding and will have these results (good or bad) come out regardless of what we gossip about here. I just feel like there is better ways to deal with things and be more proactive.

Not to mention that this isn't even a drug that mentions targeting tinnitus...

 

[FGG]

If we're doing play by play as a form of therapy, I'll add lol. I'm speaking for my own opinions only.

Obviously, I saw the 4/15 and 6/15 numbers. What I just couldn't shake, really at all, was the insane unlikelihood of seeing those huge WR responders. I still can't. Then there was the fact that the <= 90% word ceiling reduced the WR to 4/6. Of the 2/6 non-WR responders, 1 was close and the other wasn't, but they just happened to be the person in the group with the shortest duration. For the same criteria, the placebos looked exactly like placebo data: 2 insignificant improvements and 2 insignificant decreases.

Really, my bull thesis was three fold, and I almost worked under the assumption that I didn't care about multiple dosing.

1) Placebos cannot improve in WR to the level that we saw from a few people in Phase 1. I didn't consider that someone could start low from a bias to get in. Never crossed my mind.

2) Recruiters would be close enough to the hardcore responders that even though the data wouldn't be perfect, obvious group level improvements would occur. Conservatively, the results for 1x, 2x, 4x combined vs placebo would be plenty strong enough so that even if statistically significant stratification didn't occur, we would all take a deep breath and see amazing >= 1 dose results.

3) Even if we say the 4/15 >10 dB improvement at 8 kHz compared to 0/8 for placebo isn't statistically significant (it wasn't, but the p-value wasn't too bad), surely the EHF would make it based on the pharmacology study.

Really, I was the most wrong about 1) and 3) and we don't know about 2). What we do know about 2) is that even if they applied a filter and theoretically had a good, quadruple blinded process, there's just rough, unforeseen issues with study design.

I am shocked that all 3 of my thesis points were destroyed.

I can't reconcile this though. Abysmal word scores were not a requirement for Phase 1, so why would people lie?

It makes sense to do it for Phase 2 (it's shitty but it makes sense) but not Phase 1.

 

[Bill Arsenault]

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

Other way around. Lower are deeper.

 

[Princebeyel]

So did anyone find out what's next?

 

[Zugzug]

I can't reconcile this though. Abysmal word scores were not a requirement for Phase 1, so why would people lie?

It makes sense to do it for Phase 2 (it's shitty but it makes sense) but not Phase 1.

You make a fair point. The WR data from Phase 1 looked like about what you would expect.

 

[Philip83]

How is it even possible to have better word scores and no improvement in the extended audiogram? That's like having no increase in strength, but being able to lift heavier objects anyway.

Could be synapses.

FX-322 was my only hope. I have waited over 2 years, tortured to no end by tinnitus, only to learn this drug doesn't do anything or work at all, with no proper candidate to alleviate my suffering anytime soon.

I will now start putting my things in order and put an end to my suffering. It is sad it has come to this but I can't live like this.

I have heard Pegasos does accept tinnitus sufferers as potential candidates.

If you're younger than 75, don't do it. I've been dealing with this shit for 20 years now, and for every worsening that I didn't think I could bounce back from, I did. It has sometimes taken months, and for others years, but you will wake up one day and go "huh, I actually didn't think about my tinnitus almost all day today".

And my tinnitus is constantly about a 7/10 on good days, and hyperacusis is 6/10 on good days. Both are 10/10 on bad days. It's still doable.

 

[Tezcatlipoca]

So did anyone find out what's next?

Please share the screenshots of your friend that had his/her tinnitus improve.

 

[Jurger]

So did anyone find out what's next?

They'll do the seven month read out next quarter, then the read out of the two remaining Phase 1/2 trials (age related hearing loss and severe hearing loss). What's next is anyone's guess. I won't be surprised if they go back to the drawing board.

 

[Diesel]

I wonder if they could create a "multi-class" trial, where they advise patients to do the best they can, and based on those entrance results, they are put into a class, and then a random dose cohort. Each class may have slightly different outcomes, for Mild, it might focus on QoL measures, but as the hearing loss increases, the measurements change.

This would encourage people to not cheat, and they still get the same random dose opportunity.

 

[Aaron91]

I'm beginning to wonder whether a positive 210 day readout is possible. We don't actually need to see anyone in the treatment group improve further. We just need to see the placebo group go back to where the fuck they should be - baseline. But apparently that baseline was inflated due to trial design. Is there any universe in which the placebo group don't do as well second time round? I guess not if they're being "normal", right?

 

[TheDanishGirl]

If you're younger than 75, don't do it. I've been dealing with this shit for 20 years now, and for every worsening that I didn't think I could bounce back from, I did. It has sometimes taken months, and for others years, but you will wake up one day and go "huh, I actually didn't think about my tinnitus almost all day today".

And my tinnitus is constantly about a 7/10 on good days, and hyperacusis is 6/10 on good days. Both are 10/10 on bad days. It's still doable.

Maybe for you. It doesn't mean it's the same for everybody else. For me it simply is not doable.

 

[HootOwl]

I can't reconcile this though. Abysmal word scores were not a requirement for Phase 1, so why would people lie?

It makes sense to do it for Phase 2 (it's shitty but it makes sense) but not Phase 1.

I actually fear I might have been unknowingly complicit in the whole fraud thing, if that turns out to be truly legitimate. Most people were not given the reason for their rejection from the Phase 2a trial, but I was.

They point blank told me that although my audiogram qualified me, my WR scores did not, and I shared that here on the forums... my intention was to save people the hassle, money, and mental stamina of getting a HF audiogram if they (like me) had no WR issues. Because it ultimately wouldn't matter even if you had measurable notches.

But now I see why most testing sites would not disclose the reason why people were rejected... because if you knew that the WR scores were the lynch pin you could more easily lie your way into the trial.

God I feel like I really fucked up.

 

[FGG]

You make a fair point. The WR data from Phase 1 looked like about what you would expect.

It's either the unblinded individual data in Phase 2 will look a lot better (and they can compare long term medical records to see who was lying about word scores in Phase 2) for certain individuals or the patients in Phase 1 *were* somehow literally plants like Toby said but I don't see how that could have managed that without bribing testing centers and don't believe Frequency Therapeutics is a fraudulent company given the reputations of the people involved.

The other thought is that maybe word scores results are unrelated to OHCs and may reflect something like IHC preference.

It just doesn't make sense that the Phase 1 super responders would lie when there was no benefit to them to do so (unlike Phase 2).

 

[UHPTS]

They have people from one shot studies that have improved. Why wouldn't they give those people another shot to see if they get further improvement? Does everything have to happen inside the study? Can't they help designing the study by doing some experimenting on side?

Unless one shot studies were fraud which I don't believe, than FX-322 still works but as the latest study showed, four weekly consecutive shots don't work. There was just an expectation that more shots would work better than one. As they said there was no way for them to test multiple shots on animals so they did on humans and it didn't work out.

Other than craze around stocks, there isn't really much that happened. They just need to refocus to one shot or multiple shots over longer period of time.

 

[vttbx]

Dear 8k,

I just learned that I won't be able to reconnect with you and your friends in the high-frequency range. It saddens me that I will have to delay our meeting indefinitely. I do have faith that we will meet at some time in the future. Please tell everyone how much I miss them and that I think about them every day.

Sincerely,
vttbx

 

[Aaron91]

I actually fear I might have been unknowingly complicit in the whole fraud thing, if that turns out to be truly legitimate. Most people were not given the reason for their rejection from the Phase 2a trial, but I was.

They point blank told me that although my audiogram qualified me, my WR scores did not, and I shared that here on the forums... my intention was to save people the hassle, money, and mental stamina of getting a HF audiogram if they (like me) had no WR issues. Because it ultimately wouldn't matter even if you had measurable notches.

But now I see why most testing sites would not disclose the reason why people were rejected... because if you knew that the WR scores were the lynch pin you could more easily lie your way into the trial.

God I feel like I really fucked up.

I'm not going to point fingers here, nor do I hold a grudge. The people who suck are those who went and purposely deflated their baseline scores. You weren't to know that.

However, I'm wondering whether what you're saying does hold some truth, not essentially in respect of you but more generally. Didn't Lucchino say something along the lines that they learned from social media points of enquiry that patients had been sharing the WR entry criteria?

 

[Jurger]

They have people from one shot studies that have improved. Why wouldn't they give those people another shot to see if they get further improvement? Does everything have to happen inside the study? Can't they help designing the study by doing some experimenting on side?

Unless one shot studies were fraud which I don't believe, than FX-322 still works but as the latest study showed, four weekly consecutive shots don't work. There was just an expectation that more shots would work better than one. As they said there was no way for them to test multiple shots on animals so they did on humans and it didn't work out.

Other than craze around stocks, there isn't really much that happened. They just need to refocus to one shot or multiple shots over longer period of time.

There is much that happened. They found out from the second Phase 1/2 study (published today) that improvements in extended high frequency scores are absent in patients that improved their word scores. This drug doesn't do anything for the audiogram. And even in the patients that do improve (around 30% of patients), it's only around a 10% increase in word recognition.

 

[Jcmc]

I don't understand why these companies keep making the same mistake with the delivery method to the cochlea. Frequency Therapeutics, Otonomy, Pipeline.

It is no longer about if the drug works or not, it is about the delivery method to the cochlea.

If they do not work on the delivery method to the cochlea, we will always be in the same situation of failures.

 

[Zugzug]

I'm beginning to wonder whether a positive 210 day readout is possible. We don't actually need to see anyone in the treatment group improve further. We just need to see the placebo group go back to where the fuck they should be - baseline. But apparently that baseline was inflated due to trial design. Is there any universe in which the placebo group don't do as well second time round? I guess not if they're being "normal", right?

No chance of day 210 analysis being fundamentally different, in my opinion.

 

[Zugzug]

I actually fear I might have been unknowingly complicit in the whole fraud thing, if that turns out to be truly legitimate. Most people were not given the reason for their rejection from the Phase 2a trial, but I was.

They point blank told me that although my audiogram qualified me, my WR scores did not, and I shared that here on the forums... my intention was to save people the hassle, money, and mental stamina of getting a HF audiogram if they (like me) had no WR issues. Because it ultimately wouldn't matter even if you had measurable notches.

But now I see why most testing sites would not disclose the reason why people were rejected... because if you knew that the WR scores were the lynch pin you could more easily lie your way into the trial.

God I feel like I really fucked up.

It's a tough spot and certainly not your fault.

Don't get me wrong, if a drug came out for my problem and had huge potential, I don't think I would intentionally or unintentionally exaggerate anything to get in, but if I really believed there was a 75% chance of getting immediate relief from my suicidal level problem, it's not something that should be left up to the patient.

Really, I don't have an answer yet. I'm brainstorming ways to weed out lying, even if it's accidental.

 

[Xojo]

Does anyone else figure this thread will sizzle out and die like the Lenire and Audion Therapeutics ones if day 210 results are just as bad? The only drugs I remain hopeful for are Ebselen and the reformulated Trobalt.

Now I understand why veterans are so jaded towards miracle cures. It just doesn't work like that.

I remember when I was a kid hearing medical professionals warning us about protecting our ears. When we were getting one of those required hearing tests at school, one of them warned that anything close to a cure for hearing loss won't be seen in our lifetimes or even in our grandkids' lifetimes and that hearing aids would be the only treatment.

Later, in my early 20s I had to get a hearing test (my hearing was good and I didn't have any tinnitus) at my job and I asked one of the audiologists about how far off we are from a possible cure and he estimated five hundred years or so. I thought that estimate was absurd at the time and there that for sure there would be unexpected medical breakthroughs that they weren't considering. When I first heard about Frequency Therapeutics, I thought those professionals were finally going to be proven wrong, but sadly, I guess not. More worrisome is that I'm starting to consider that they may actually be right and I am just a dreamer giving my hopes up for an impossible pie-in-the-sky cure.