Frequency Therapeutics — Hearing Loss Regeneration

[hopetohear]

Hi all, I'm new here but have been following Tinnitus Talk in hope for the past 6 months.

I'm mainly concerned with the hearing regeneration component and I'm wondering what people's thoughts are regarding what type of hearing loss FX-322 will treat and what testing will be needed to back this up before possibly being treated with FX-322? E.g., will it only be for noise induced hearing loss? Or also genetic hearing loss?

Will we need thorough genetic testing beforehand getting the treatment? If so, I'm hoping to get the ball rolling now so I am prepared if this all goes ahead!

 

[frpp]

Hi all, I'm new here but have been following Tinnitus Talk in hope for the past 6 months.

I'm mainly concerned with the hearing regeneration component and I'm wondering what people's thoughts are regarding what type of hearing loss FX-322 will treat and what testing will be needed to back this up before possibly being treated with FX-322? E.g., will it only be for noise induced hearing loss? Or also genetic hearing loss?

Will we need thorough genetic testing beforehand getting the treatment? If so, I'm hoping to get the ball rolling now so I am prepared if this all goes ahead!

Most likely an audiogram, preferably an extended one, will suffice, even if you have genetic hearing loss (provided it is SNHL), FX-322 should still help you.

 

[weab00]

Hi all, I'm new here but have been following Tinnitus Talk in hope for the past 6 months.

I'm mainly concerned with the hearing regeneration component and I'm wondering what people's thoughts are regarding what type of hearing loss FX-322 will treat and what testing will be needed to back this up before possibly being treated with FX-322? E.g., will it only be for noise induced hearing loss? Or also genetic hearing loss?

Will we need thorough genetic testing beforehand getting the treatment? If so, I'm hoping to get the ball rolling now so I am prepared if this all goes ahead!

Noise-induced hearing loss only, since it treats cochlear damage and not genetic mutations that cause congenital hearing loss. With that in mind, no gene testing is required since the people going into this treatment know they have noise-induced tinnitus/hearing loss. Though an audiogram will probably be required.

 

[Lucifer]

Remember FX-322 can also get Breakthrough Therapy status as well. I am not too sure how quickly they can release FX-322 once they get Breakthrough Therapy status.

 

[hopetohear]

Noise-induced hearing loss only, since it treats cochlear damage and not genetic mutations that cause congenital hearing loss. With that in mind, no gene testing is required since the people going into this treatment know they have noise-induced tinnitus/hearing loss. Though an audiogram will probably be required.

I hope there is room for genetic loss to be considered for treatment also. I guess it might depend on how the genetic loss is manifested too, whether through hair loss or more nerve related. I'm not sure how that is discovered though.

 

[RB2014]

Most likely an audiogram, preferably an extended one, will suffice, even if you have genetic hearing loss (provided it is SNHL), FX-322 should still help you.

I think the general consensus is that if you were born with all of your hearing and the hearing loss is genetic, as in you lost your hearing faster than normal due to defective genes, then FX-322 will probably work. It won't fix the underlying problem and you will still lose hearing at a faster rate due to the genetic defect. This hasn't been proven though, but we are hoping.

As a side note, even a genetic fix, like CRISPR, would only be effective at birth to stop the hearing loss. Re-writing the genes after you have lost your hearing won't get your hearing back...

If you have genetic hearing loss and it is from birth because things were formed incorrectly, then FX-322 will not work.

So it depends on what is meant by genetic hearing loss.

 

[Margus]

So by completing trials in the US first, Frequency Therapeutics will have done what is required to release the medicine in the US under both the compassionate use provision and to get the final FDA approval.

This means Frequency Therapeutics can start selling the treatments in the US as soon as possible, obtain their payment from Astellas for running the trials in Asia and Europe and still successfully comply with the overall requirements to fulfil the FDA process.

Therefore I think that it is truly possible that Frequency Therapeutics might release FX-322 after phase 2a providing it actually satisfies the FDA requirements.

While Frequency Therapeutics will get in trouble if they directly comment that they are going to release FX-322 through compassionate access, we know they have indicated many times and through many platforms that they have a clear desire to help people as quickly as possible. Furthermore I feel that Frequency Therapeutics have certainly laid the framework to potentially be able to release FX-322 early after the current trial is done.

So I would say that an early release post phase 2a does currently seem to be very possible.

Here is what Expanded Access (compassionate use) means:

Expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

I really don't see how FX-322 could qualify here. Besides even if a medicine is approved for expanded access it doesn't mean everyone can get it or it is somehow released without undergoing all three phases of the clinical trial. Basically compassionate use means that someone who is terminally ill could get access to a drug that is still being trialed.

 

[serendipity1996]

And yet the study results unfortunately are not proving it so far. Let's hope for the best for Phase 2a, but I think the fact they have started look into hidden hearing and tinnitus as possible new secondary outcome targets is sign of desperation. You wouldn't need that if you have a confidence to achieve primary target.

Here is what Expanded Access (compassionate use) means:

Expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

I really don't see how FX-322 could qualify here. Besides even if a medicine is approved for expanded access it doesn't mean everyone can get it or it is somehow released without undergoing all three phases of the clinical trial. Basically compassionate use means that someone who is terminally ill could get access to a drug that is still being trialed.

I recall Frequency Therapeutics mentioning that in their discussions with the FDA, they had said that although hearing loss is not 'life-threatening', it can be profoundly life-altering - recent research has also implicated it as a significant risk factor for neurodegenerative diseases, e.g. dementia.

 

[FGG]

Here is what Expanded Access (compassionate use) means:

Expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

I really don't see how FX-322 could qualify here. Besides even if a medicine is approved for expanded access it doesn't mean everyone can get it or it is somehow released without undergoing all three phases of the clinical trial. Basically compassionate use means that someone who is terminally ill could get access to a drug that is still being trialed.

Quality of life altering diseases qualify too, not just terminal.

The fact that Frequency Therapeutics has mentioned considering Compassionate Use on both their website and the Tinnitus Talk Podcast and the fact that they have Fast Track Designation (which means they are already regularly meeting with the FDA and would understand the FDA's positions on their drug) leads me to believe the drug does legally qualify.

 

[Street Novelist]

Does everyone get FX-322 in Phase 3 or will some people still get the placebo?

 

[Gb3]

Noise-induced hearing loss only, since it treats cochlear damage and not genetic mutations that cause congenital hearing loss. With that in mind, no gene testing is required since the people going into this treatment know they have noise-induced tinnitus/hearing loss. Though an audiogram will probably be required.

They are testing for sudden sensorineural hearing loss and SSHL, not just noise induced.

 

[Gb3]

Hi all, I'm new here but have been following Tinnitus Talk in hope for the past 6 months.

I'm mainly concerned with the hearing regeneration component and I'm wondering what people's thoughts are regarding what type of hearing loss FX-322 will treat and what testing will be needed to back this up before possibly being treated with FX-322? E.g., will it only be for noise induced hearing loss? Or also genetic hearing loss?

Will we need thorough genetic testing beforehand getting the treatment? If so, I'm hoping to get the ball rolling now so I am prepared if this all goes ahead!

 

[tommyd87]

You raise some very good points on the potential accessibility of FX-322 after Phase 2a. As a counterpoint, the primary issue would be the findings of the study from only 95 participants.

Given the limited variability of audiogram scores after treatment, the cost factors for the procedure, and possibly hindering any conclusive strong backing that a Phase III would probably provide, I believe Frequency Therapeutics will elect to proceed with Phase III given the financial backing that was received from investors in August, 2020 for the sole purpose of financing further testing. This company is hell bent on leaving no stone unturned and patience is key.

Frequency Therapeutics gets payment from Astellas for running a trial in Asia and Europe. I am pretty sure that Frequency Therapeutics can utilise those results to satisfy their phase 3 trial requirements.

I think that Frequency Therapeutics will engage in further testing. However I believe that this further testing will be outside of the required FDA trials and actually won't have any bearing on whether they can actually release FX-322 via compassionate access.

This additional testing will probably focus on testing FX-322 with other potential user groups like seniors and those with just say mild hearing loss, in order to expand the sale-ability of FX-322.

If Frequency Therapeutics can demonstrate to relevant stakeholders who can benefit from FX-322 using supporting evidence, then it is more likely that relevant parties who can drive FX-322 sales like ENTs will recommend it to many more people. Furthermore this will help Frequency Therapeutics to convince potential users more broadly that FX-322 will work for them too, hopefully convincing them to look into FX-322 and therefore inevitably convincing them to spend the money to buy it.

Frequency Therapeutics knows that they currently have a significant consumer market available from those who presently require and also desire treatment. The issue that Frequency Therapeutics has now is to expand the scope of sales to attain a better return on investment. The simplest way of expanding markets with medicinal treatment is to provide evidence of who the treatment works with, as people want to be certain that what they are buying is beneficial and not simply a waste.

Thus I still feel that Frequency Therapeutics will endeavour to get FX-322 released ASAP providing they can satisfy the requirements of the FDA. However I believe their key focus post release is going to be about expanding the market in order to gain more use and sales too.

 

[tommyd87]

Here is what Expanded Access (compassionate use) means:

Expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

I really don't see how FX-322 could qualify here. Besides even if a medicine is approved for expanded access it doesn't mean everyone can get it or it is somehow released without undergoing all three phases of the clinical trial. Basically compassionate use means that someone who is terminally ill could get access to a drug that is still being trialed.

The FDA is actually very focused on both granting expanded access and fast tracking access to treatments. From memory there has been a bipartisan push for this from both sides of politics and there has been more medicines and treatments fast tracked now than ever before.

Thus I think that if FX-322 is successful (and same with any other hearing related treatments) then the FDA would be very willing to grant this Fast Track status.

Yes, a medicine does require completing all FDA trial requirements, however this has no bearing on whether compassionate access will be granted and also actually provides a fair indication that the medicine is significantly beneficial.

Does everyone get FX-322 in Phase 3 or will some people still get the placebo?

All trials operate in the same fashion. So some will get placebo and some will get FX-322.

 

[wwtsai]

I hope there is room for genetic loss to be considered for treatment also. I guess it might depend on how the genetic loss is manifested too, whether through hair loss or more nerve related. I'm not sure how that is discovered though.

As someone that's had hearing loss since my teens, this question has definitely come up more than once for me. If you read over articles covering FX-322, a lot of them state it probably won't help with genetic hearing loss. You're right in that genetic hearing loss manifests itself in many different ways; generally those that deal with something else besides hair cells such as the mitochondria or Na-K channels also include other serious health conditions as those are not specific to just the cochlear. I do plan to do a genetic test at some point to see if I have any mutations of genes related to hearing. Regardless of the results, I also plan to undergo FX-322 treatment whenever that time comes.

 

[Street Novelist]

The FDA is actually very focused on both granting expanded access and fast tracking access to treatments. From memory there has been a bipartisan push for this from both sides of politics and there has been more medicines and treatments fast tracked now than ever before.

Thus I think that if FX-322 is successful (and same with any other hearing related treatments) then the FDA would be very willing to grant this Fast Track status.

Yes, a medicine does require completing all FDA trial requirements, however this has no bearing on whether compassionate access will be granted and also actually provides a fair indication that the medicine is significantly beneficial.

All trials operate in the same fashion. So some will get placebo and some will get FX-322.

Then I don't get it. If Phase 3 will also have a placebo, what's the point of a Phase 3? Just more people? So it wouldn't be beneficial to try to get into the next trial. I guess we hope they just release it after this phase.

 

[tommyd87]

As someone that's had hearing loss since my teens, this question has definitely come up more than once for me. If you read over articles covering FX-322, a lot of them state it probably won't help with genetic hearing loss. You're right in that genetic hearing loss manifests itself in many different ways; generally those that deal with something else besides hair cells such as the mitochondria or Na-K channels also include other serious health conditions as those are not specific to just the cochlear. I do plan to do a genetic test at some point to see if I have any mutations of genes related to hearing. Regardless of the results, I also plan to undergo FX-322 treatment whenever that time comes.

I think that the development of the medicine has drastically altered the way things are looked at with hearing loss. This includes the ways which hearing loss can be treated, what works to treat it and also actually what techniques can be used to treat it.

I also would like to see the reasons why these researchers can claim that FX-322 is not going to work with certain people. As far as I am aware, if you can regrow synapses and hair cells then there is no reason that you would not actually benefit from this medicine either.

 

[tommyd87]

Then I don't get it. If Phase 3 will also have a placebo, what's the point of a Phase 3? Just more people? So it wouldn't be beneficial to try to get into the next trial. I guess we hope they just release it after this phase.

The trouble is that even in phase 3 trials, companies like Frequency Therapeutics still need to demonstrate that the medicine works, the medicine delivers the intended outcomes and that there is no placebo effect.

While it might seem largely pointless to be basically repeating the phase 2 trial with larger numbers of participants, it is necessary to demonstrate that the medicine works with a very big cohort in order to validate its effectiveness.

It doesn't matter that ear medicines and specifically hearing medicines can demonstrate their effectiveness with a small cohort. This is because all medicines are required to follow the same FDA rules to obtain approval to get it released.

Therefore it is quite possible that the following things will happen regarding trial progression and the release of FX-322:

1. If the current trials demonstrate that FX-322 is effective, Frequency Therapeutics will probably be able to apply for compassionate use allowance from the FDA. It is probable that the FDA could grant compassionate use to Frequency Therapeutics because it would appear FX-322 would satisfy the relevant criteria.

2. If Frequency Therapeutics obtains compassionate use then FX-322 could be released after the current trial. This is very possible since Frequency Therapeutics said they would consider applying to obtain compassionate use from the FDA and then granting this to potential FX-322 users.

Frequency Therapeutics would however still be required to take FX-322 through the phase 3 trial process to satisfy FDA requirements completely.

3. Frequency Therapeutics would commence the overseas trials in Asia and Europe. These trials would be recognised by the FDA as being compliant with the phase 3 trial requirements. Frequency Therapeutics would also satisfy the agreement they have with Astellas to conduct and complete trials in Asia and Europe. Provided the FDA declares these phase 3 trial as satisfactory, Frequency Therapeutics would then be able to release the medicine globally and also freely.

While it does seem stupid and it does suck that Frequency Therapeutics need to take FX-322 through a phase 3 trial, this is completely necessary to satisfy the FDA requirements. Furthermore it will prevent those against FX-322 or any other hearing medicine being able to make claims which question its safety or challenge its effectiveness for nefarious purposes.

Thus while the FDA process is protracted, it is ultimately going to ensure that the medicine is effective, safe and most importantly enables it to be used.

At this point in time, I think that Frequency Therapeutics has set things up well and laid the groundwork to possibly get its medicine FX-322 released early in some jurisdictions under the compassionate use rules.

 

[SallyM]

New FX-322 phase 1b trial, this time for age-related sensorineural hearing loss:

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

Locations in Florida, Nebraska, New York, Texas and Virginia recruiting. Total number of participants: approx 30.

Tinnitus mentioned in the secondary outcome measures.

 

[weab00]

New FX-322 phase 1b trial, this time for age-related sensorineural hearing loss:

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

Locations in Florida, Nebraska, New York, Texas and Virginia recruiting. Total number of participants: approx 30.

Tinnitus mentioned in the secondary outcome measures.

Showing that they have faith that this will work for tinnitus. Very good sign.

 

[Diesel]

New FX-322 phase 1b trial, this time for age-related sensorineural hearing loss:

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

Locations in Florida, Nebraska, New York, Texas and Virginia recruiting. Total number of participants: approx 30.

Tinnitus mentioned in the secondary outcome measures.

Interesting that they put the C-SSRS as a measurement in the primary outcome. Obviously we all know hearing loss sucks, and it must be tough to be aging and losing your hearing...

Perhaps this is an indication that they've received anecdotes that a single dose of FX-322 has improved quality of life for prior trial participants?

 

[GlennS]

Showing that they have faith that this will work for tinnitus. Very good sign.

Very small trial group, though. Kind of sad that Neuromod had such a large trial group and yet had such a lackluster outcome in the real world.

 

[tommyd87]

Interesting that they put the C-SSRS as a measurement in the primary outcome. Obviously we all know hearing loss sucks, and it must be tough to be aging and losing your hearing...

Perhaps this is an indication that they've received anecdotes that a single dose of FX-322 has improved quality of life for prior trial participants?

There are three parts to this:

1. This trial is a safety study only since Frequency Therapeutics still needs to go through the same processes for this cohort like with any other trial. Essentially I think that the only reason Frequency Therapeutics are doing a single dose is because of the rules around safety trials require this.

2. I think that C-SSRS indication which is being tested tends to be the thing that will enable Frequency Therapeutics to obtain insurance coverage for age related hearing loss. Literally the major reason that Frequency Therapeutics would be doing this trial would be to hopefully obtain insurance coverage for this group. The ability to satisfy the requirements to obtain insurance coverage for this group would be huge for Frequency Therapeutics from a revenue perspective as successful treatment for this group is going to give them their biggest number of potential customers.

3. This is purely a guess, however I wonder whether Frequency Therapeutics is reasonably confident in the medicine's effectiveness in the main trial? Something tells me that they wouldn't be investing money in further trials while their current trial is still running if they didn't feel that their medicine was not effective and not demonstrating benefit and that the additional trials weren't also a worthy investment.

 

[Gb3]

Is this separate from the current trial? Will this prolong the outcome of the pending trial? If this age-related hearing loss trial is successful, will this expedite approval?

 

[Diesel]

Is this separate from the current trial? Will this prolong the outcome of the pending trial? If this age-related hearing loss trial is successful, will this expedite approval?

Separate from the SNHL trial. Not likely to cause delays. Probably won't expedite approval for SNHL. Will enable FX-322 to be used to treat age-related hearing loss if successful.

May help in the Breakthrough Therapy indication.

May by a lesser degree help in compassionate use debate.

 

[tommyd87]

Separate from the SNHL trial. Not likely to cause delays. Probably won't expedite approval for SNHL. Will enable FX-322 to be used to treat age-related hearing loss if successful.

May help in the Breakthrough Therapy indication.

May by a lesser degree help in compassionate use debate.

I think that the current SNHL trial is going to be what influences and determines whether FX-322 gets given compassionate access and breakthrough status too. The thing is Frequency Therapeutics just need to demonstrate that FX-322 meets the criteria for effectiveness and compassionate use once and can do this through the current trial providing the medicine works effectively.

Something tells me that this trial for age related hearing loss is to enable FX-322 to gain insurance coverage and nothing else for the age related cohort. Currently there is nothing stopping FX-322 being prescribed off-label for age related hearing loss once it has been approved by FDA. Thus this indicates to me that this trial has nothing to do with medicine approval as it is simply going to have no bearing on that. Thus Frequency Therapeutics is simply seeking to get the medicine covered through insurance to make access easier for age related hearing loss patients. This will also be a big win for Frequency Therapeutics because it will expand sales significantly since the cost of the medicine and treatment cost will be covered by insurance. This is ultimately going to mean that there then will be bigger revenue obtained by Frequency Therapeutics which will theoretically in turn mean greater profitability.

 

[Diesel]

Separate from the SNHL trial. Not likely to cause delays. Probably won't expedite approval for SNHL. Will enable FX-322 to be used to treat age-related hearing loss if successful.

May help in the Breakthrough Therapy indication.

May by a lesser degree help in compassionate use debate.

Actually, now that I read more about it... the outcome of the C-SSRS may be helpful in the argument that hearing-loss is a life-threatening/life-altering disorder. Should the data show a significant decrease in the C-SSRS assessment score, this would fulfill another Breakthrough Designation requirement.

 

[Margus]

Perhaps the latest trial is a very good sign. We know from phase 2a that all participants are enrolled and by now most likely they have already got all 4 injections. It would be insane to start yet another safety trial (just like phase 1a) to target older people if you know that it doesn't work in young. They must be seeing FX-322 works in phase 2a participants and want to expand its use to older population.

 

[Born To Slay]

I think that the current SNHL trial is going to be what influences and determines whether FX-322 gets given compassionate access and breakthrough status too. The thing is Frequency Therapeutics just need to demonstrate that FX-322 meets the criteria for effectiveness and compassionate use once and can do this through the current trial providing the medicine works effectively.

Something tells me that this trial for age related hearing loss is to enable FX-322 to gain insurance coverage and nothing else for the age related cohort. Currently there is nothing stopping FX-322 being prescribed off-label for age related hearing loss once it has been approved by FDA. Thus this indicates to me that this trial has nothing to do with medicine approval as it is simply going to have no bearing on that. Thus Frequency Therapeutics is simply seeking to get the medicine covered through insurance to make access easier for age related hearing loss patients. This will also be a big win for Frequency Therapeutics because it will expand sales significantly since the cost of the medicine and treatment cost will be covered by insurance. This is ultimately going to mean that there then will be bigger revenue obtained by Frequency Therapeutics which will theoretically in turn mean greater profitability.

Would you mind explaining how the insurance thing works here? As far as I know, insurance companies still cover drugs that off label as long as it's on their drug formulary. Many of the most common prescribed drugs in America are more often then not prescribed for off label purposes. Doesn't insurance cover this prescription?

 

[Born To Slay]

Perhaps the latest trial is a very good sign. We know from phase 2a that all participants are enrolled and by now most likely they have already got all 4 injections. It would be insane to start yet another safety trial (just like phase 1a) to target older people if you know that it doesn't work in young. They must be seeing FX-322 works in phase 2a participants and want to expand its use to older population.

I also think that the safer the drug is shown to be, the sooner it can get release. If it shows no side effects in any population treated, that'd make a good case to the FDA to grant breakthrough therapy status.