Frequency Therapeutics — Hearing Loss Regeneration

Mmm... some minor adjustments in your response:

Short Interval Multi-dosing: No.
Long Interval Multi-dosing: Maybe.
Single dose for Audiograms: No.
Long Interval for Audiograms: Maybe.
Speech improvements for the right patient: Maybe.

 

ClinicalTrials.gov for severe hearing loss group just got updated.

They are still recruiting...

Also completion date has been pushed towards September 2021...

This was supposed to be completed and data being analyzed by now!

Oh lord help us all... I can't hear bad news any longer.

I am telling you, the candidates whom they enrolled did not show response... They are now looking to try their chances with others... ouch!

ClinicalTrials.gov: FX-322 in Adults With Severe Sensorineural Hearing Loss

 

Wrong. The trial dates are revised because they haven’t been able to recruit enough participants to reach the enrollment target.

 

Take a deep breath. I’m quite sure this isn’t how clinical studies work.

 

So since November 2, 2020 they haven't been able to find 30 candidates from any of these cities: Michigan, Nebraska, New York, South Carolina, Texas, Virginia...

Ok, cool, I respect your opinion...

Can someone living nearby in any of the below cities enroll for their severe hearing loss studies? Clinical Trials Information Desk 800-839-9241.

I posted same warning last year when they suddenly started new Phase 1 trials in the middle of Phase 2a, but I was was turned off by some users... I know something is not right...

 

With all due respect, this is conspiracy theory level thinking.

 

Something I've been wondering lately. Since both hair cells and synapses are important for hearing, wouldn't it be interesting to test treating a combination of both to see if it works better?

I know Frequency Therapeutics doesn't have a drug to restore synapses, but Otonomy is working on separate drugs to restore both hair cells and synapses.

 

I covered the enrollment challenge a couple pages back, but I'll write it again:

Challenges with Enrolling in this trial:

- Candidates have to be at a regularly scheduled appointment with the an ENT/Audiologist at a practice that is also a testing site where they are referred to the trial, or they need to contact that number listed above, of which they'll be referred to the local practice that is performing the trial. There's no advertising permitted for trials like this, so the broad public is not made aware of this type of trial.

- It appears that most people with hearing loss at that level go to the doctor annually for a checkup, unless an event warrants it. So, a candidate for this trial will need to be at a participating doctors office in one of the cities listed during the recruiting period, and referred to the trial.

- The patient is then provided information on the trial, risks, what they're committing to. And are often advised to do their own homework before agreeing to proceed.

- After submitting paperwork/medical history and probably doing some type of "interview" for the trial. The trial administrators can decide whether the candidate meets inclusion criteria for the trial.

- The patient has to then agree that having an experimental drug / placebo injected into their ear is worth the risk (potentially making their hearing worse, or getting nothing out of it), along with committing to follow-up appointments for the successive 90-day period. This means they'll need reliable transportation to the trial site, and can allocate a potential 2-3 hours per assessment visit.

- After all of that happens just right and everything is agreed upon, then they are enrolled into the trial.


So, as you can see from this, enrollment has a lot working against it: timing, patient acceptance of risk, commitment, and the administrator accepting them into the trial.

In conclusion, I would argue that they've probably become extremely strict about enrolling the "perfect" candidate into the trial after the Phase 2A didn't go as expected. So, the enrollment is probably taking longer than expected.

If we want to talk about "Lessons Learned from the Phase 2A" don't we agree that it would be beneficial to get the enrollment to the trial right to better understand the ideal patient / effectiveness of the drug, even if it means a 3-month delay?

 

Thank you @Diesel for your input, I appreciate the time you always take answering posts from members...

I also really want this to work!

 

I don't see how they can plan on doing more trials this year if the severe trial doesn't end until September. Wouldn't they have to release the results of the severe trial before starting another one?

 

Do you remember the CEO who said in February that the Phase 3 will start in December 2021 when he already knew that the Phase 2A was a failure?

I'm not saying this to be pessimistic.

But don't put hope in a company like this. Since March 23, it's been a succession of bad news, without end.

There are too many red flags to believe in FX-322.

 

Amen. I'm not prepared to speak out of both sides of my mouth. I will not criticize management for being slow to get it right.

 

Severe trial is estimated to end in September, meaning readout will only be by November 2021.

That's IF they have finished recruiting now... which apparently is not the case because they are still looking for candidates to inject with FX-322...

 

An important point:

About the open label study of Phase 2A:

33% of people had 10% or more improvement. It's literally the results of the placebo; where are the real improvements?

FX-322 doesn't work, I don't see any other explanation.

The 3 super responders of Phase 1 have no value when we know how bad Frequency Therapeutics is at designing a clinical trial.

 

Agreed... Those are pretty strict. Even with my extreme hearing loss I don't go every year to get tested. My hearing loss is happening much faster than most, to be almost deaf at 48, but even then it has been a pretty stable loss over the years.

They are trying to keep the company going and see where this ends up. They need to see if they can make a case to use FX-322 for some types of hearing losses. As we've said previously, the results were not what they expected.

 

I’ve been absent from the forum for some months. To sum up the recent developments:

1. There was a bad Phase 2 trial result.
2. It’s not clear that research with FX-322 will continue at all.
3. Frequency Therapeutics are gettin’ sued.

Is this more or less the gist of it? It would be helpful for people to have a summary post.

 

Sorry but the Phase 2a was not an open label study... Everyone agrees that Phase 2a was a failure...

The 3 super responders from Phase 1/2 is questionable...

The improvements from Phase 1 moderate open label study is being claimed as legit...

 

Yes, I'm talking about the study where 33% of participants had at most 10% improvement with a single dose.

Here is my question, I would like to understand if I'm wrong somewhere:

The results of this study are no different from Phase 2A, there was no placebo control, so it was impossible to prove that it was FX-322 that did something.
In addition, in Frequency Therapeutics' tests, the placebo always improves.

The argument that multiple doses are the root of the problem is no longer valid.
Single dose didn't do better than multiple doses when comparing Phase 2A to the open label.

Add to this that the 3 super responders are questionable, there is no evidence that FX-322 ever worked on a human.

Where am I wrong? I would like to understand if I missed something.

 

You got many things mixed up.

I'm using my phone so I'll try to be as clear and brief as possible:

Phase 1/2 is being claimed as successful, it was placebo controlled, and had good responders. But the issue here is that this study was done way before they learnt their lesson about bias candidates, so this is why I consider it as questionable.

Phase 2a was placebo controlled, but failed because of 2 things:

1) multi dose (short intervals) doesn't work
2) many bias candidates where they faked their hearing test in order to enter the trial, so everything got messed up.

Frequency Therapeutics believe single dose works, so they did an open label (not placebo-controlled) study Phase 1 for moderate hearing loss and they claim it as successful.

I am attaching here the results for both, Phase 1/2 and the Phase 1 open label study:

 

This is the problem:

This single dose study didn't have a placebo control. But the results were no better than the placebos in Phase 2a.

I repeat: 33% improvement to 10% or more is no better than placebo. They have no way of knowing if this improvement is due to the FX-322 or the placebo.

These results are in the field of the placebo.

 

You cannot take or compare anything from Phase 2a.

Phase 2a does not have a verified baseline from anyone, so please stop considering Phase 2a with anything.

Phase 2a is just a complete garbage. If you don't have verified baseline from either placebo or candidates who took the drug, then it's just zero value.

As for the open label of moderate (not placebo-controlled) Phase 1, all the candidates know they are getting the drug so they have less bias/incentive to lie in hopes of getting it.

So in this open label, they claim many got good results...

 

If Phase 1 wasn’t a fluke and those patients did have improvements in audiograms and word scores, then I expect the Phase 2 repeat should be the same with only single dosing of FX-322.

 

Yes, those patients had improvement in word scores only.

With current formulation and delivery method no audiogram improvement was ever recorded till date.

In future studies, Frequency Therapeutics wants to try multiple doses far away from each other to see if it provides better results in terms of word recognition and audiogram.

 

All that hope for this shit.

What a f*cking disappointment.

 

I feel not everyone is understanding what's happening, here is an example:

Michael and Laura are desperate to get FX-322, so they both apply for the Phase 2a trials:



Michael in reality can hear 30 words out of 50, but as he is desperate, he fakes his initial screening to get into the trial by telling the doctor he can only hear 15 words out of 50.

Laura in reality can hear 35 words out of 50, but tells the doctor she can only hear 20 out of 50:



The doctor is happy he found good candidates for the trial. He gives Michael the placebo, and Laura gets the drug (FX-322):



After the trial is completed, the doctor gets the results:



The doctor saw that Laura improved! She used to hear 20 words out of 50 and now after getting the drug, she can hear 35 words out of 50! The doctor is happy!

Michael was never given the drug but also improved? Michael now hears 30 words out of 50.

So what does the doctor do now?

He basically just claims that Michael was a bias... and he is happy that Laura improved!

Are you guys getting the point?

Michael and Laura never improved, their real scores stayed the same the whole time.

 

Thomas... are you okay...?

I think you need a chill pill

 

That’s an excellent example, but let me demonstrate why I complain about this criteria to get accepted into the trial.

To enter the trial, you needed 4 or 8 words out of 20 or 30.

This is a different scenario. You can’t fake the words unless you get extremely lucky. You have to repeat the word back, not just say you heard it.

If I heard 1 word, I could’ve been given the drug or the placebo. If I heard 2 words next week (repeated back), you’d have your answer whether it does something or not with future testing in the following weeks.

If I heard 0 words, it would be the same scenario, so it doesn’t make sense to have these limitations unless they feel there’s not enough hearing for the drug to do anything. I’d still be willing to give it a shot.

Let me point that out again for those who complain patients falsified the trial, you have to repeat the word back and get the word correct to enter the trial.

 

Ok, that's the pessimistic view. In reality Laura may have improved to now hear 40 words.

But because Michael "improved" with placebo there is no statistically significant improvement with the drug.

There is no point trying to read into the numbers because we don't know who was faking or not in both groups.

The saving grace is that all groups that received the drug saw some benefit in their word scores. Imagine if there was no benefit from the drug but there was from placebo. In that case FX-322 would be dead.