Frequency Therapeutics — Hearing Loss Regeneration

According to the August presentation, there is "Significant enthusiasm amongst <Otolaryngology> community." So, I'm sure there is some awareness... however, greater reach and frequency of the messaging means new eyeballs on the firm and the clinical trials.

 

They all had the same dose in phase 1.

Did they say that someone who had a statistically significant increase in word scores, then had a drop?

 

Maybe I'm misinterpreting something, but the study "Arms and Interventions" section indicates that there was a high dose group and a low dose group in Phase 1/2:

https://clinicaltrials.gov/ct2/show/NCT03616223

As for the second question, yes. They allude to it by saying "three of which remained at statistically significant levels". The 4th person still had a "hearing benefit", but it was no longer statically significant. They also talk about this briefly in the Goldman Sachs webcast [1, timestamp: 12:23] they did a few months ago. There they say the 4th person fell just outside the bounds of statistical significance. However, it's unclear if they were on the border of significance in the first place, or if they had a reasonable drop.

[1] https://kvgo.com/GSHC/frequency-therapeutics-june-2020

 

There definitely were two dose categories, a low dose and a high dose, in the initial Phase 1/2 trial.

I thought that there were six people who were showing statistically meaningful word improvements, however only four had an actual audiogram improvement. I do know that one of the four with both audiogram improvement and word improvement had fallen below the statistically significant levels.

I am also sure that they are using only the high dose from phase 1/2 in the phase 2a clinical trials.

 

Of the total number of patients Frequency Therapeutics is going to recruit for Phase 2a clinical trial, I thought 75% had already enrolled.

Can’t they just release the results of those already enrolled patients early?

I thought the FDA allowed them to conduct the clinical trials with fewer people? If 50% to 75% of the patients have already reached the 210 days after they got the FX-322 injection, can’t they still consider this viable for the Phase 2a clinical trials and go onto Phase 3 clinical trials without needing to wait for those 25%?

 

Hmm... I agree it definitely distinguishes "high dose group" and "low dose group" but they never seem to parse that out in their results unless I missed something...

I wish they could release all of the individual data so we could see who got what doses and what their word scores and audiograms were (as in patient A had this word score and this audiogram) though I realize clinical trial results are never reported that way for any trial I have seen (I wonder why? Is that somehow a HIPAA thing?).

We don't even know which people improved at 8 kHz in terms of their word scores.

 

Another half a year delay with strange wording. Either the criteria is too stringent, the FDA is too slow or it takes too long to find trial candidates.

I met the criteria and was denied entry twice into this trial. The process was already slow before COVID-19.

Something in the process has to change to get some results. Trial 100 people after safety is established, no matter the hearing loss, report if hearing has improved or not.

 

looks like we'll have to be ever more patient. I just hope that this stuff works. I'm just learning to cope with my disease now. It'll make restoration that much sweeter.

 

I'm now more than a little concerned.

Fine, there is a delay related to COVID-19, but why such a long one? Maybe there has been a delay for other reasons that is not being brought to light and that just happens to fit in with the delay due to the virus?

Conspiracy theories.

 

There was a low dose group and a high dose group in Phase 1/2. The high dose is being used for Phase 2a.

 

Have you been given a reason why you we’re not wanted as a trial participant? It indicates to me that you must have actually been rejected because there was some reason or some factor that they didn’t want you for outside of the criteria related to hearing.

As far as I am aware the FDA has nothing to do with the trial's progression. Rather they simply oversee that what the Pharma company is doing complies with FDA’s requirements and assesses the trial results to determine approval of the treatment.

I’m sure that there is some reason behind why Frequency Therapeutics decided this specific set of eligibility criteria.

As for the delay, I definitely don’t think that this is unreasonable nor is the reasoning strange. I just think that they’re trying to complete the trial using the required numbers. It is inevitably going to take time due to what needs to happen.

I think that this is a conspiracy theory. There was a fair acceptance and idea that there would be some delay from fairly early on during this trial.

I think that Frequency Therapeutics wouldn’t withhold reason(s) for delays in the trial if they were anything other than the virus related delays. It seems that they have been very transparent in their approach to things. Therefore this would be a huge step backwards for them in terms of their goodwill and trustworthiness if they were not being upfront about this.

 

I do remember them saying that there was no significant difference in outcomes between the two groups. This was in the supporting documentation for the IPO.

 

Yes I was, my word score was about two words too low to get in. How does two words make a difference in knowing if the drug works or not?

You see it took the trial site a very long time to find a candidate that fit their criteria, months after my denial to get one in. That was before COVID-19. Since I have severe hearing loss I can’t try Otonomy either. There needs to be some way to get more people to do trials, make them aware of them.

Where’s the numbers of how many people tried to get in and how many were denied?

To push even further everyone on here should be posting about their numerous attempts to enter these trials, how else is a cure found?

 

They said in their Fireside that they had a temporary pause in their enrollment but were still dosing and following already enrolled participants. Since they are following people for 5 months out, a small delay in enrollment leads to having to wait 5-6 months out from those enrolled later. It's totally feasible that that's what happened. No need for conspiracies to explain it.

 

It's a long one because Frequency is probably forecasting out to when they think a vaccine might be available to be safe. At the rate COVID-19 is going in America, it's liable to really slow things down for testing across the board. Might be better to have some Canadian testing sites in the future so if any global pandemic happens at least some movement can be made.

 

Does anyone have experience with FDA trials? This is a double blind study in which neither the patients nor Frequency Therapeutics know the results during the trials. Some independent third party is collecting the data. If anyone has experience on FDA trials and can tell us if and only if Frequency Therapeutics gets the results from such third party once the trial is 100% completed or unless the trial is aborted due to severe safety issue.

If this is the case, there's no point guessing why Frequency Therapeutics is doing this or that at 50% enrollment or something else.

 

Just out of curiosity, what was your word score? If it was really bad, they may think there aren't enough support cells left to regenerate sufficient hearing.

 

I didn't know either until someone on this forum pointed it out. If you do a google search of `"high dose" site:frequencytx.com`, only 1 result comes back, and it doesn't give any useful information. I've read the same thing that d'Wooluf posted, but I can't find any outside documentation to back it up. I've also read that they went with the high dose for Phase 2a, but that's another thing I can't find any outside documentation on. I would be weary about believing anything without an outside source, as sometimes this forum can act like an echo chamber. Looking back through the thread, at one point people were saying the dose in Phase 2a would be higher than Phase I/II [1], but I can't find anything to back that up either.

I speculate that at least 3 of the 4 responders had a high dose. And now that @Piney has mentioned that he was rejected for too low of a word score, I wonder if improving high frequency hearing loss has its limits with helping word scores. Maybe those with really low word scores didn't see statistical improvements in Phase I/II even if they had a high dose. @Piney did they tell you what your word score out of 50 was?

Carl LeBel specifically mentioned trying to recruit people like the "4 responders" for Phase IIa. I think they want really good results for Phase 2a, so they're trying to replicate what happened in those 4 people across a study of 96 people.

That's a good point. I'd just assumed they were the same 4 that had word score improvements, but they never state that anywhere. One thing Carl said in the Goldman Sochs conference that was interesting was that there was a "ceiling" effect to improvement [2, timestamp: 11:34]. I wonder if people from the "mild" hearing loss group couldn't achieve statistical improvements in word score because their scores were already too high. Maybe it was people from this group that saw improvements at 8 kHz.

[1] https://www.tinnitustalk.com/threads/frequency-therapeutics-—-hearing-loss-regeneration.18889/page-198#post-489070
[2] https://kvgo.com/GSHC/frequency-therapeutics-june-2020

 

It’s possible that they could’ve conducted the trial with fewer people, but this would almost certainly mean that an additional phase would be required prior to approval.

By allowing for a delay, they have time to fully meet their desired trial population and gather more data. This will provide a better shot of obtaining Breakthrough Therapy status, which would be the best-case scenario for everyone (earlier approval).

 

The ceiling effect is intuitive, if you already have near perfect word scores, it is hard to get an improvement.

@Piney, are you sure they rejected you because of word score alone? If i recall correctly, you were a cochlear implant candidate which would put you above the 70dB range of their trial.

 

Yup, I remember we discussed this sometime ago. I always counted on a delay given that they have to follow patients 210 days and are still enrolling.

 

It's highly likely it's the same 4 patients that had the word score improvements.

I have suspected that they may not be inclined to show too much about the individual patients because it could be used to skew the recruits in the Phase 2A. Imagine being an patient or ENT and seeing the audiograms in the presentation; you might think "hey I'm the perfect candidate" or "I'm absolutely not right." Where in reality, it should be up to the investigator on the trial.

I believe it was @FGG that mentioned a while back that there may be an internal acceptance criteria in addition to what is displayed on the clinical trial website. Which might explain why potential candidates are being rejected, even though they believe they pass all the acceptance requirements.

In order for Frequency to get Breakthrough Status, prove the drug works, and get it into the market; the Phase 2A data needs to show statistical significance on the primary outcomes. This means being extremely selective; and having hearing loss that they believe shows the best chance for statistical improvement within the scope of the trial.

 

Dosage details for FX-322's Phase 1: https://clinicaltrials.gov/ct2/show/NCT03616223

Excluding the placebo, they had a single dose for 16 patients: eight had low dose and eight had high dose.

For specific word scores, it's here: https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

Excluding the placebo, they reported 15 patients even though clinical trials detailed a total of 16. Perhaps one patient discontinued for whatever reasons. The graph in the above frequencytx.com's link show word scores for all 6 patients with a dashed line demarcating the 4/6 patients that they think is significant. If someone says there's only 3/4 remaining significant, I wonder which patient became insignificant then...

@tommyd87 The above link does show word scores so you were right.

 

Maybe with this delay there is a slight chance for them to release FX-322 out in the market after the Phase 2a clinical trial finishes.

 

I think I got 6 right but I needed 8, I believe 20%. The only reason I missed them was my tinnitus was loud.

We need to ask how many people fail to get into these trials because of tinnitus? You can’t hear your best when your ear is blaring. Why don’t the companies relax the criteria because of this. I’m in the 70 dB range of hearing loss for longer than 6 months, therefore I cannot get into any trials. It’s a problem. Why would I donate to something I can’t take the risk on. This needs to be mentioned and questioned on. For those of you who can get into the trials, Godspeed and good luck, you're the only hope on the patients' end.

The point is even with FX-322 there are always delays and always excuses why reports can be pushed back years. If the system worked there wouldn’t be these problems. I’m starting to see a think tank mentality to all of this, create the hype, soar the stock, sell the shares.

Next Tinnitus Talk Podcast should be about telling these companies to open their criteria and produce some real results.

I hope I’m wrong, I hope greed hasn’t reached that level.

 

What are the odds that someone could be rejected for having Visual Snow Syndrome?

 

I think that a fair part of it comes down to the desire and need to show that the treatment has benefit or can show benefits during the trial. This doesn’t mean it won’t work for you, it simply says that in the trial scenario(s) you might not provide the necessary results to demonstrate effectiveness.

 

What did you mean by "I got 6 right but I needed 8"? Are you referring to word scores count?

I'm so sorry you couldn't get in. To be honest, all these delays do not inspire confidence but it could just be me and many sufferers are already depressed and cynical about past companies being failures and even worst scams. Only thing we can do is just hope they're sincere in making money by delivering a legit product.

 

Their exclusion criteria has listed over 70 dB as an exclusion from the start (it is on their clinicaltrials.gov page). I'm not sure why that specifically was the cut off but I doubt they would change their entire parameters (not sure they would even be allowed to since the trial as outlined is approved by the FDA before start) because of COVID-19 or other enrollment delays.

Frequency is also not taking public donations that I am aware of.

 

Next to none considering I applied and was not asked about it and it is not on their exclusion list.