Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

I cannot see where what you have stated about the Norvartis trial is listed on the Clinical Trials page, sorry.

It's under "detailed description":

https://clinicaltrials.gov/ct2/show/NCT02132130

"The study will evaluate the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients are required to have documented, non-fluctuating hearing loss. Part A and Part B enrollment is complete. Part C enrollment is open."

 

[tommyd87]

It's under "detailed description":

https://clinicaltrials.gov/ct2/show/NCT02132130

"The study will evaluate the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients are required to have documented, non-fluctuating hearing loss. Part A and Part B enrollment is complete. Part C enrollment is open."

Interesting.

I know that @serendipity1996 reported that they were looking at redoing the treatment at some point and as a result I wonder whether this relates to that.

The other thing is it could be an error.

 

[kiki]

Phase 3 is generally largely a comparison to the "standard of care" and I'm not sure how that would work with this drug but another component of phase 3 is larger safety study for more rare side effects.

Is there a Phase 2 element in Phase 2b / 3?
Isn't the purpose of Phase 2 to study more effective dosing methods?

 

[Princebeyel]

It's under "detailed description":

https://clinicaltrials.gov/ct2/show/NCT02132130

"The study will evaluate the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients are required to have documented, non-fluctuating hearing loss. Part A and Part B enrollment is complete. Part C enrollment is open."

Is this similar to what FX-322 is doing?

 

[FGG]

Is there a Phase 2 element in Phase 2b / 3?
Isn't the purpose of Phase 2 to study more effective dosing methods?

They are doing phase 2a now with multiple dose cohorts.

 

[FGG]

Is this similar to what FX-322 is doing?

Not really, no.

 

[tommyd87]

Is this similar to what FX-322 is doing?

Completely different method.

 

[tommyd87]

Cool, so this basically is backing up the repeat dosage method that Frequency Therapeutics is hoping will work... which at least gives more confidence that it's not just a blind, hopeful suggestion.

I would assume that the multiple injection method would work better if the 4 injections were given in the same sitting, like using the last injection to push the prior injection further.

Just my crude, uneducated thought. I understand that the theory is that each shot is soaked up by the first damaged part it comes in contact with, which clears the way for the next shot to go deeper 2 weeks later... I would just assume that pushing more of the drug deeper would work and cover the whole cochlea in one sitting.

More of the medicine would definitely go further into the ear. Essentially there is no way where Frequency Therapeutics could do a larger single dose without retrialling it for safety.

I think that the lab work demonstrates larger dosing could be effective, especially because it was shown to be the case in the rat trial which will obviously need less medicine than a person will. I think that the 4 doses in one sitting is definitely a good way which we can see Frequency Therapeutics get around the FDA safety retesting requirements which they would be stuck with if they went with just a single dose.

 

[Street Novelist]

Does anyone have extreme anxiety to the point it's affecting your sleeping and day-to-day activities or is it just me? I don't know how much longer I can take this. Even if they release the results in May, when would the next trial start? Can anyone venture a guess?

 

[patorjk]

A thought occurred to me today. In one of Otonomy's press releases, they mentioned that they had "successfully escalated through three dose levels totaling 24 patients and have nearly completed enrollment of patients in the high dose cohort" for OTO-413. I may be interpreting this incorrectly, but it sounds like they're doing their Phase I/II dosage testing incrementally in groups.

I wonder if this is standard and what Frequency Therapeutics is doing too. 96 patients (their original goal) would break-up nicely into 3 groups of 32. Each of these groups could have 8 placebo patients. If they were to do it this way, then it would mean they have completed the first dosage group (1 dose of FX-322), and that the other two groups were still in progress (2 doses and 4 doses).

The end result of the study would be the same, but doing it this way would have the following consequences:

* Interim results would not be possible, as the most important group would not finish until the end of the study.
* The study would have to enroll a number of patients near its set goal of 96.

Could this be how Frequency Therapeutics' study is setup? If so, it would mean that only recently has anymore been given 4 doses of FX-322.

[1] https://investors.otonomy.com/news-...rts-second-quarter-2020-financial-results-and

 

[Diesel]

A thought occurred to me today. In one of Otonomy's press releases, they mentioned that they had "successfully escalated through three dose levels totaling 24 patients and have nearly completed enrollment of patients in the high dose cohort" for OTO-413. I may be interpreting this incorrectly, but it sounds like they're doing their Phase I/II dosage testing incrementally in groups.

I wonder if this is standard and what Frequency Therapeutics is doing too. 96 patients (their original goal) would break-up nicely into 3 groups of 32. Each of these groups could have 8 placebo patients. If they were to do it this way, then it would mean they have completed the first dosage group (1 dose of FX-322), and that the other two groups were still in progress (2 doses and 4 doses).

The end result of the study would be the same, but doing it this way would have the following consequences:

* Interim results would not be possible, as the most important group would not finish until the end of the study.
* The study would have to enroll a number of patients near its set goal of 96.

Could this be how Frequency Therapeutics' study is setup? If so, it would mean that only recently has anymore been given 4 doses of FX-322.

[1] https://investors.otonomy.com/news-...rts-second-quarter-2020-financial-results-and

Assignment is randomized. It's possible they could release an interim analysis, but those are more likely in multi-year Phase 3s.

It's much more likely for them to release information/results of an independent short-term study on the effects of FX-322 on age-related or severe hearing loss.

It would be fairly straightforward to recruit a small group of patients for the above hearing losses and study how FX-322 affects their hearing after 90 days.

 

[Lucifer]

A thought occurred to me today. In one of Otonomy's press releases, they mentioned that they had "successfully escalated through three dose levels totaling 24 patients and have nearly completed enrollment of patients in the high dose cohort" for OTO-413. I may be interpreting this incorrectly, but it sounds like they're doing their Phase I/II dosage testing incrementally in groups.

I wonder if this is standard and what Frequency Therapeutics is doing too. 96 patients (their original goal) would break-up nicely into 3 groups of 32. Each of these groups could have 8 placebo patients. If they were to do it this way, then it would mean they have completed the first dosage group (1 dose of FX-322), and that the other two groups were still in progress (2 doses and 4 doses).

The end result of the study would be the same, but doing it this way would have the following consequences:

* Interim results would not be possible, as the most important group would not finish until the end of the study.
* The study would have to enroll a number of patients near its set goal of 96.

Could this be how Frequency Therapeutics' study is setup? If so, it would mean that only recently has anymore been given 4 doses of FX-322.

[1] https://investors.otonomy.com/news-...rts-second-quarter-2020-financial-results-and

Good point. Maybe that's why those earlier patients did not notice improvements as they may have only got 1 dose of FX-322 and the other 3 shots were placebo, or no FX-322 dose at all.

 

[FGG]

Good point. Maybe that's why those earlier patients did not notice improvements as they may have only got 1 dose of FX-322 and the other 3 shots were placebo, or no FX-322 dose at all.

That was a pretty low information anecdote which:

A) could have been placebo
B) didn't provide proof
C) provided no audiogram info
D) reported this right after when the effects may take weeks to months after injection to be realized.

In birds, natural regeneration takes 4 weeks:

http://www.cochlea.eu/en/research-lines/regeneration

I wouldn't try to interpret that any which way.

 

[FGG]

A thought occurred to me today. In one of Otonomy's press releases, they mentioned that they had "successfully escalated through three dose levels totaling 24 patients and have nearly completed enrollment of patients in the high dose cohort" for OTO-413. I may be interpreting this incorrectly, but it sounds like they're doing their Phase I/II dosage testing incrementally in groups.

I wonder if this is standard and what Frequency Therapeutics is doing too. 96 patients (their original goal) would break-up nicely into 3 groups of 32. Each of these groups could have 8 placebo patients. If they were to do it this way, then it would mean they have completed the first dosage group (1 dose of FX-322), and that the other two groups were still in progress (2 doses and 4 doses).

The end result of the study would be the same, but doing it this way would have the following consequences:

* Interim results would not be possible, as the most important group would not finish until the end of the study.
* The study would have to enroll a number of patients near its set goal of 96.

Could this be how Frequency Therapeutics' study is setup? If so, it would mean that only recently has anymore been given 4 doses of FX-322.

[1] https://investors.otonomy.com/news-...rts-second-quarter-2020-financial-results-and

Everyone gets 4 doses of *something* in the FX-322 trial. From none to 4 doses of drug. If it's truly randomized, there wouldn't be a pattern except that you get more drug at 4 weeks than 1 week if you are part of the 4 dose cohort.

Otonomy are perhaps measuring each dose versus placebo because it is their first trial (and not second as Frequency Therapeutics' is), and they have less idea of optimal dosing and need to test each dose vs placebo. I can't think of another reason to do it that way since it is less randomized.

 

[Lucifer]

That was a pretty low information anecdote which:

A) could have been placebo
B) didn't provide proof
C) provided no audiogram info
D) reported this right after when the effects may take weeks to months after injection to be realized.

In birds, natural regeneration takes 4 weeks:

http://www.cochlea.eu/en/research-lines/regeneration

I wouldn't try to interpret that any which way.

It wasn't just one anecdote though. There was another which was mentioned in this thread.

If @patorjk's theory is true then the patients that they just recruited recently could be the ones who are getting 4 doses of FX-322.

 

[tommyd87]

A thought occurred to me today. In one of Otonomy's press releases, they mentioned that they had "successfully escalated through three dose levels totaling 24 patients and have nearly completed enrollment of patients in the high dose cohort" for OTO-413. I may be interpreting this incorrectly, but it sounds like they're doing their Phase I/II dosage testing incrementally in groups.

I wonder if this is standard and what Frequency Therapeutics is doing too. 96 patients (their original goal) would break-up nicely into 3 groups of 32. Each of these groups could have 8 placebo patients. If they were to do it this way, then it would mean they have completed the first dosage group (1 dose of FX-322), and that the other two groups were still in progress (2 doses and 4 doses).

The end result of the study would be the same, but doing it this way would have the following consequences:

* Interim results would not be possible, as the most important group would not finish until the end of the study.
* The study would have to enroll a number of patients near its set goal of 96.

Could this be how Frequency Therapeutics' study is setup? If so, it would mean that only recently has anymore been given 4 doses of FX-322.

[1] https://investors.otonomy.com/news-...rts-second-quarter-2020-financial-results-and

I think that the trial method being done by Otonomy for the OTO-413 trial is actually also the same as what FX-322 did in their first trial, though the reality is that Otonomy is likely to get a better result from the phase 1 trial with OTO-413 since synapses seem much easier to deal with.

Otonomy is doing a multi dose trial like they need to with safety requirements and are then trying to see that the big dose provides bigger benefit. Then in phase 2 they will probably test OTO-413 to see that it does indeed work effectively with the larger group of people so it is eventually able to be released.

 

[FGG]

It wasn't just one anecdote though. There was another which was mentioned in this thread.

If @patorjk's theory is true then the patients that they just recruited recently could be the ones who are getting 4 doses of FX-322.

Frequency Therapeutics is definitely not doing dose escalation this trial. I have the paperwork from when i applied and it outlined exactly how the dosing schedule was. I posted it before but I can look for it again and repost tomorrow.

I forgot about the 2nd anecdote. The same still applies.

 

[all to gain]

Does anyone think it's feasible we could get FX-322 in Q3/Q4 of next year if all goes well?

No.

 

[tommyd87]

It wasn't just one anecdote though. There was another which was mentioned in this thread.

If @patorjk's theory is true then the patients that they just recruited recently could be the ones who are getting 4 doses of FX-322.

Randomised trial. There's as big of a chance of the first patient having gotten 4 doses of placebo as the last patient.

I am pretty positive that the only time dose escalation is done is in the phase 1 trial when you are actually required to show that the treatment is safe at different doses.

 

[d'Wooluf]

Does anyone have extreme anxiety to the point it's affecting your sleeping and day-to-day activities or is it just me? I don't know how much longer I can take this. Even if they release the results in May, when would the next trial start? Can anyone venture a guess?

If you're not getting direct help for your anxiety, go get it. If you're getting anxious over the possible results of the FX-322 trials, maybe you should take a break from this thread. If you can't do that, check in once a week. Obsessing over it won't make things happen any quicker and it may be making you more miserable. There's no chance of you missing the news when it's released. (Sincere advice given with good intentions).

 

[tommyd87]

No.

Why not? If Frequency Therapeutics gets good outcomes from their trial, why wouldn't they be pushing to get FX-322 released ASAP? Especially when Frequency Therapeutics has got the chance to be the first to release their treatment and will actually have a significant advantage over Otonomy etc by having their treatment out for a year or so without any actual competition?

Does anyone think it's feasible we could get FX-322 in Q3/Q4 of next year if all goes well?

I think that this is entirely possible, especially if Frequency Therapeutics can get FDA approval and can get FX-322 made and out to the relevant parties.

Personally I wouldn't be surprised if Frequency Therapeutics pushed for a quick release because they will have an advantage over others by having their treatment released first. Also even if there was a slight delay I could still see Frequency Therapeutics pushing for FX-322 to come out ASAP as I don't think that there would be so much forward planning being done or even consideration of organising things like pricing if it isn't going to be something which isn't going to need to be resolved in the near future.

 

[tommyd87]

Everyone gets 4 doses of *something* in the FX-322 trial. From none to 4 doses of drug. If it's truly randomized, there wouldn't be a pattern except that you get more drug at 4 weeks than 1 week if you are part of the 4 dose cohort.

Otonomy are perhaps measuring each dose versus placebo because it is their first trial (and not second as Frequency Therapeutics' is), and they have less idea of optimal dosing and need to test each dose vs placebo. I can't think of another reason to do it that way since it is less randomized.

Simply safety. Seeing the FDA rules relating to clinical trials, there is a requirement that you escalate the dose sizes to prove that the treatment is safe at different strengths. Otonomy can consequently also test the treatment effect and benefit at the same time. The logic indicates that they know the big dose is best but they too may actually get an unexpected outcome from a smaller dose.

 

[d'Wooluf]

Why not?

Because best case scenario is that Frequency Therapeutics and FDA agree that the next trial is 'pivotal'. Even if that trial is no longer than phase 2a and takes about as long to organise, it's at least a year. Phase 2a enrolled its last participant almost 2 years after phase 1b finished.

 

[tommyd87]

Because best case scenario is that Frequency Therapeutics and FDA agree that the next trial is 'pivotal'. Even if that trial is no longer than phase 2a and takes about as long to organise, it's at least a year. Phase 2a enrolled its last participant almost 2 years after phase 1b finished.

You can actually release a medicine and also run the pivotal phase at the same time. This has been demonstrated before with other compassionate access medicines and treatments.

 

[d'Wooluf]

You can actually release a medicine and also run the pivotal phase at the same time. This has been demonstrated before with other compassionate access medicines and treatments.

Carl LeBel said that if the results warranted, they would discuss the possibility of the next trial being pivotal with the FDA. He didn't say anything about a possible release of the drug after this trial. Compassionate use could happen now if Frequency Therapeutics wanted to make it available. That's not the same as releasing the drug.

Do you really think there's a chance that you could go to an ENT in Melbourne in December next year and get FX-322 when they finish their first efficacy trial in May? Hope you're right then.

 

[Serouj]

You can actually release a medicine and also run the pivotal phase at the same time. This has been demonstrated before with other compassionate access medicines and treatments.

You're right, but FX-322 isn't any medicine. I don't think that they would take any chances unless they are 100% ready to launch it into the market. It's the first of its kind.

 

[kiki]

They are doing phase 2a now with multiple dose cohorts.

That was the case.
The results of Phase 2a that are currently underway are important now.

And we don't know if the next phase will be Phase 2b, Phase 3, or Phase 2b / 3, and we don't know what it will be like right now.

It is important to move forward step by step. In this marathon, I will accumulate short-distance goals and finish the final goal...

I can't see the goal, but I can feel it.

The place where you can listen to your discussions gives you the energy to run without dents.

 

[all to gain]

Why not? If Frequency Therapeutics gets good outcomes from their trial, why wouldn't they be pushing to get FX-322 released ASAP? Especially when Frequency Therapeutics has got the chance to be the first to release their treatment and will actually have a significant advantage over Otonomy etc by having their treatment out for a year or so without any actual competition?

I'll believe it when I see it.

No way is this drug hitting the market next year. I would love to be wrong though.

 

[Diesel]

While I am hopeful that Frequency Therapeutics will allow compassionate use after the Phase 2A; I am unclear of the strategy.

Phase 3 will still need filled with viable recruits, who may or may not receive placebo; while compassionate use gives them direct access to the drug.

How will Frequency Therapeutics provide access via compassionate use while also committing to filling a Phase 3 in a reasonable timeframe? Will they require that patients that are fit for the Phase 3 be directed to the clinical trial and denied compassionate use.

Will compassionate use be extremely strict where only the absolute, verifiable worst cases get access to the drug?

 

[FGG]

While I am hopeful that Frequency Therapeutics will allow compassionate use after the Phase 2A; I am unclear of the strategy.

Phase 3 will still need filled with viable recruits, who may or may not receive placebo; while compassionate use gives them direct access to the drug.

How will Frequency Therapeutics provide access via compassionate use while also committing to filling a Phase 3 in a reasonable timeframe? Will they require that patients that are fit for the Phase 3 be directed to the clinical trial and denied compassionate use.

Will compassionate use be extremely strict where only the absolute, verifiable worst cases get access to the drug?

The only way they accept compassionate use and not have a recruitment delay is to have a very large international pool for phase 3, but I think it's possible.

Otherwise, their trial might mostly include people who couldn't afford the drug and would have at least some delay.