Frequency Therapeutics — Hearing Loss Regeneration

[AfroSnowman]

Is the consensus that FX-322 regrows both the OHCs and the IHCs or just OHCs?

 

[Ozwel]

Not necessarily going to be longer. One thing that is believed to be happening is the Phase 2a trial might be determining whether FX-322 shows good enough results after 90 days to demonstrate appropriate benefit or whether they need to go the full 7 months.

Therefore there is a reasonable likelihood that this will make Phase 3 shorter if they only need to wait 90 days to show results, even if the results are better after 7 months. Not to mention there won't be the delays in Phase 3 around things like recruiting and coronavirus which pushed this trial out further.

I may be missing something; why would recruitment be easier for Phase 3?
By the way would there be any Phase 4 to expect?

 

[scotty03874]

• The Phase 2a day-90 readout will assess all efficacy and safety endpoints following single or multiple doses of FX-322, or placebo.

I was looking for the end of Phase 2a since I couldn't find it in the last pages. So just in case, sharing it here again: summer 2021 at best. Will Phase 3 last even longer? I guess so... in that case no treatment would be available for everyone in the US before 2023-24.

• FX-322 Phase 2a study of patients with mild to moderately severe acquired SNHL (ages 18-65): The Phase 2a study completed enrollment with 95 patients in September 2020. The Company today announced plans to provide a complete analysis of day-90 Phase 2a study data, which is anticipated late in Q1 2021. The Phase 2a end-of-study (seven month) readout is anticipated late in Q2 2021.

Source: Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis - Frequency Therapeutics (frequencytx.com)

Do you think that there is any possibility that FX-322 will be available outside of the USA before it's actually available here in the United States?

 

[serendipity1996]

Is the consensus that FX-322 regrows both the OHCs and the IHCs or just OHCs?

Yes it regrows both.

 

[Diesel]

Is the consensus that FX-322 regrows both the OHCs and the IHCs or just OHCs?

From Carl LeBel at Frequency Therapeutics: Both OHC and IHC are regrown.

 

[tommyd87]

I may be missing something; why would recruitment be easier for Phase 3?
By the way would there be any Phase 4 to expect?

Phase 4 does not exist.

Essentially Phase 3 is hopefully easier to recruit for because Frequency Therapeutics will have a wider range of subjects to choose from.

 

[Diesel]

I may be missing something; why would recruitment be easier for Phase 3?
By the way would there be any Phase 4 to expect?

Why recruiting for Phase 3 may be more "efficient":

1. Greater patient/doctor population awareness of FX-322 due of positive Phase 2A results. May be via the news media and/or Frequency Therapeutics communication with doctors/patients, or other general comms methods.

2. US & International Trial Sites providing access to a larger population. The FDA may allow for more sites for the Phase 3 in the US. Astellas has agreed to run Phase 3 clinical trial sites in EU / ASIA / Others.

3. Phase 2A results will include Safety Data. If patients and doctors feel the drug is safe; more will be likely to apply.

4. Speculation: The Phase 3 may only need a 90-day "Assessment Period" making it easier for patients to commit to the trial; and more likely to apply.

5. Speculation: Phase 3 may not be as "selective" as the Phase 2A; making it easier for a wider range patients to be accepted.

6. Speculation: FDA Breakthrough Therapy Designation.

 

[FGG]

By the way would there be any Phase 4 to expect?

I'm sure there will be a Phase 4, but it's a post approval monitoring study so it won't affect the wait.

 

[Billy_Shears]

Looking forward to Phase 5... in my ENT Physician's office, both ears!

 

[Philip83]

Why recruiting for Phase 3 may be more "efficient":

1. Greater patient/doctor population awareness of FX-322 due of positive Phase 2A results. May be via the news media and/or Frequency Therapeutics communication with doctors/patients, or other general comms methods.

2. US & International Trial Sites providing access to a larger population. The FDA may allow for more sites for the Phase 3 in the US. Astellas has agreed to run Phase 3 clinical trial sites in EU / ASIA / Others.

3. Phase 2A results will include Safety Data. If patients and doctors feel the drug is safe; more will be likely to apply.

4. Speculation: The Phase 3 may only need a 90-day "Assessment Period" making it easier for patients to commit to the trial; and more likely to apply.

5. Speculation: Phase 3 may not be as "selective" as the Phase 2A; making it easier for a wider range patients to be accepted.

6. Speculation: FDA Breakthrough Therapy Designation.

Do you think it's possible we will know something about a potential Phase 2 or Phase 3 study outside of US from Astellas during 2021?

 

[Gb3]

Is the consensus that FX-322 regrows both the OHCs and the IHCs or just OHCs?

It depends how deep the formula can get.

 

[Diesel]

Do you think it's possible we will know something about a potential Phase 2 or Phase 3 study outside of US from Astellas during 2021?

Based on other international Phase 3s, it'll be announced all at once.

 

[Jack V]

I'm sure there will be a Phase 4, but it's a post approval monitoring study so it won't affect the wait.

The majority of experimental drugs do not get FDA approval. Let's HOPE there is a Phase 4!

 

[FGG]

It depends how deep the formula can get.

Inner doesn't mean "deeper."

There are 3 rows of outer hair cells and 1 row of inner hair cells across the entire length of the cochlea.

 

[FGG]

The majority of experimental drugs do not get FDA approval. Let's HOPE there is a Phase 4!

Though obviously I can't guarantee it, it seems very likely to me FX-322 will get approved (so far safe, effective, unmet need). I don't think it's possible to fake what they have already accomplished.

So, in that case, there will be a post market Phase 4 monitoring study as is standard for FDA approved drugs.

Most of us probably won't wait for completion of Phase 4 to try FX-322, though, since it would be available after approval before then.

 

[Philip83]

Based on other international Phase 3s, it'll be announced all at once.

Hm, ok. I'm sure I read something about a payout-milestone from Astellas to Frequency Therapeutics when they dose the first person in a Phase 2 (a or b) in Europe.

 

[Gb3]

I don't think it's going to work. I was optimistic but I think it will help hearing but not like we think it will.

 

[Princebeyel]

I don't think it's going to work. I was optimistic but I think it will help hearing but not like we think it will.

Why do you think this?

 

[Gb3]

Why do you think this?

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

 

[Jack V]

Though obviously I can't guarantee it, it seems very likely to me FX-322 will get approved (so far safe, effective, unmet need). I don't think it's possible to fake what they have already accomplished.

So, in that case, there will be a post market Phase 4 monitoring study as is standard for FDA approved drugs.

Most of us probably won't wait for completion of Phase 4 to try FX-322, though, since it would be available after approval before then.

I too believe approval is likely, but many drugs demonstrate safety, efficacy, and unmet needs in Phase I and II only to flame out in Phase III.

For example, AM-101:

https://www.genengnews.com/news/aur...didate-keyzilen-fails-second-phase-iii-trial/

That said, Frequency Therapeutics is a far more impressive, well-funded team, FX-322 has a lot of positive momentum, and I'd personally squirt some in my ears with a turkey baster if given a chance.

However, there's a misunderstanding in this thread that FX-322 has been proven "100% safe" based on early trials with a limited number of people suffering severe hearing loss.

Expanded to 1,000 or 10,000 or 100,000 people with moderate or mild hearing loss, or tinnitus sufferers with normal non-extended audiograms, we don't know what side effects, potential hearing damage, or efficacy findings might show up.

AM-101 was pulled mid-Phase III for lack of efficacy. Betaserc received FDA approval only to have it withdrawn after its efficacy was "de-established" in the US (although it remains available elsewhere, go figure).

It's not necessarily fakery, it's just the nature of drug development, with trials expanding into increasingly larger populations, generating increasingly meaningful and granular data.

 

[hopes]

All drugs are in phase 4 once released.

 

[Jack V]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

I was under the impression the company had reports that it helped with tinnitus and was studying it.

*flashback to weab00's graphic*

 

[Pre55ure]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

When my ears worked I didn't have tinnitus. Now that they don't - I do.

There's lots of examples of improvements to hearing helping to reduce tinnitus, no reason to think this would be different.

 

[serendipity1996]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

But Carl LeBel said that they have already had anecdotal reports of tinnitus improvement from participants (when they have gone to see the ENT). What do you think is needed to address tinnitus then?

 

[FGG]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

 

[weab00]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

Why not? The theories for tinnitus line up with hearing loss, it makes sense that you'd lose part of your hearing by going to loud events and lose the high frequency cells.

What's a more plausible theory?

 

[patorjk]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

Someone can correct me if I'm wrong, but I don't believe FX-322 had any effect on speech in noise in the Phase I/II trial, it only improved the Word Recognition Score. The theory right now is that damage to synaptic connections is what causes speech-in-noise hearing loss. Though we'll have a better idea if that's true within the next month (when the OTO-413 results come in).

There were already reports of improved tinnitus from the Phase I/II trial. My gut assumption is that in the next 1-5 years we're going to learn that there is no single cause or solution to tinnitus. Fixing hair cells will cure some, fixing synaptic connections others, etc etc.

 

[tommyd87]

Hm, ok. I'm sure I read something about a payout-milestone from Astellas to Frequency Therapeutics when they dose the first person in a Phase 2 (a or b) in Europe.

This is why it's thought that there will be a Phase 2b/Phase 3 combined trial as members like @FGG and @Diesel have pointed out. That way it is going to enable Frequency Therapeutics to get paid for their two trials obligations and also enable them to complete the final phase trial too.

 

[serendipity1996]

It would be nice if people actually added some kind of explanation or justification for their pessimistic hot-takes lol.

 

[Diesel]

Someone can correct me if I'm wrong, but I don't believe FX-322 had any effect on speech in noise in the Phase I/II trial, it only improved the Word Recognition Score. The theory right now is that damage to synaptic connections is what causes speech-in-noise hearing loss. Though we'll have a better idea if that's true within the next month (when the OTO-413 results come in).

There were already reports of improved tinnitus from the Phase I/II trial. My gut assumption is that in the next 1-5 years we're going to learn that there is no single cause or solution to tinnitus. Fixing hair cells will cure some, fixing synaptic connections others, etc etc.

FX-322 showed improvement in word-in-noise, of 20% over baseline. But, with a p-value of .211, it's not statistically significant. So, either the sample size was too small or the ceiling effect was a factor.