Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

Attached below is a link and snapshot to an article (Wall Street Journal) describing drug approval. There is a chance that the drug can go to market after phase 2.

Fast-Track Drug Approval, Designed for Emergencies, Is Now Routine

Interesting article. I had originally thought that the Breakthrough Therapy designation might enable to drug to be released to the market after Phase 2. Based on this article; and that Frequency Therapeutics is ending essentially 3 trials in 2021; that could be enough to get early approval.

 

[FGG]

Interesting article. I had originally thought that the Breakthrough Therapy designation might enable to drug to be released to the market after Phase 2. Based on this article; and that Frequency Therapeutics is ending essentially 3 trials in 2021; that could be enough to get early approval.

My hunch is they are going to do a 2b/3 combined pivotal phase including European participants and age-related hearing loss sufferers.

 

[weab00]

My hunch is they are going to do a 2b/3 combined pivotal phase including European participants and age-related hearing loss sufferers.

And what is your opinion on compassionate use?

 

[FGG]

And what is your opinion on compassionate use?

I have no idea. I think it bodes well that they realize their drug applies and that they want to revisit it but I couldn't begin to give an odds ratio on that.

 

[tommyd87]

Attached below is a link and snapshot to an article (Wall Street Journal) describing drug approval. There is a chance that the drug can go to market after phase 2.

Fast-Track Drug Approval, Designed for Emergencies, Is Now Routine

View attachment 41282

I certainly thought that this was a pretty pertinent possibility and that there tended to be much more willingness from the FDA to approve medicines quickly which were effective and meaningful.

These treatments like FX-322 or SPI-1005 are not another paracetamol and as a result they most probably will fall into the FDA criteria relating to both fast tracking and compassionate access.

My hunch is they are going to do a 2b/3 combined pivotal phase including European participants and age-related hearing loss sufferers.

I wouldn't be shocked by this at all as effectively it is going to kill two birds with one stone by doing both trials simultaneously. Also it is going to be a lot easier to drum up the required participant numbers as well.

Still the big question is how well controlled COVID-19 will be in Europe. There is a good chance it will be controlled well by the middle of next year and probably sooner since there seems to be a big willingness and desire for countries to get it under control now. I think that this shouldn't have too much impact on trials.

The other thing is weren't Frequency Therapeutics supposed to run an Asian trial too for phase 3?

 

[Rubenslash]

You don't know that. Let's stay positive.

There's a difference between staying positive and false hope. It just won't happen, that's a 100% sure.

 

[weab00]

Something that gives me more confidence of this working for tinnitus is that Dr. McLean, a co-founder of Frequency Therapeutics, said this 2 years ago (nothing that we don't already know, just more confirmation from one of the founders):

As I mentioned, increased input from a hearing aid helps most patients. Thus, increasing input in the cochlea (if that is the cause in a given person) may help. Regenerating hair cells can increase input into the system similar to a hearing aid, but by regenerating the underlying biology that drives input. And remember, we are losing hair cells throughout our life starting at high frequencies most audiologists do not test. Hearing loss can go undetected in tinnitus sufferers, but most people with hearing loss have tinnitus. However, this is not ALWAYS the case.

My general thought is that tinnitus is a phantom limb of the ear, but instead of having sensations of touch or pain, your brain is trying to fill in lost auditory stimulation. Over activity may be a cause in some instances. I doubt there will be a 1 approach fix for the various causes of tinnitus, so based on assessment, potentially by non-standard measures, different patients may need different approaches to fix the issue.

 

[Koz]

For anyone desperate for compassionate use and release as early as next year, I am hopeful for both myself and you.

However, if this is not the case and we have to wait a bit longer, please keep in mind that there are others that have possibly had it longer and worse than you (and me). We're in this together and will support one another in our wait.

Like I said in my previous post, for me personally once they release their phase 2 results and the results meet or exceed expectations then that is half the burden off my shoulders and it is just a matter of waiting to reach the inevitable finish line. That's a massive psychological boost on its own.

I don't think 2021 is reasonable. 2022 is optimistic. 2023 is reasonable.

The issue with FX-322 is that it regenerates off the back of support cells. The question is how many support cells do you need to regenerate which is why they did moderate hearing loss because basically it ensures that there is enough support cells to regenerate hair cells.

There is going to be a trial for severe hearing loss at some point as Frequency Therapeutics have since announced this. There tends to not be enough support cells to restore a full profound hearing loss, however there are actually some other options that potentially will deal with this.

I believe OTO-6XX has already stated their compound has potential to benefit patients with severe hearing loss (if FX-322 does not, so there's that to consider if I'm not mistaken). So I have my eyes on them as well, they don't seem that far behind Frequency Therapeutics given they just signed an exclusive license agreement in August.

 

[tommyd87]

There's a difference between staying positive and false hope. It just won't happen, that's a 100% sure.

I think that this tends to be a matter of wait and see either way. We cannot answer that definitively either way at this present point.

 

[Street Novelist]

There's a difference between staying positive and false hope. It just won't happen, that's a 100% sure.

Do you have insider information? Because if you do, the rest of us would love to hear it!

 

[tommyd87]

For anyone desperate for compassionate use and release as early as next year, I am hopeful for both myself and you.

However, if this is not the case and we have to wait a bit longer, please keep in mind that there are others that have possibly had it longer and worse than you (and me). We're in this together and will support one another in our wait.

Like I said in my previous post, for me personally once they release their phase 2 results and the results meet or exceed expectations then that is half the burden off my shoulders and it is just a matter of waiting to reach the inevitable finish line. That's a massive psychological boost on its own.

I don't think 2021 is reasonable. 2022 is optimistic. 2023 is reasonable.

I believe OTO-6XX has already stated their compound has potential to benefit patients with severe hearing loss (if FX-322 does not, so there's that to consider if I'm not mistaken). So I have my eyes on them as well, they don't seem that far behind Frequency Therapeutics given they just signed an exclusive license agreement in August.

I think that Otonomy has got to the filing the IND stage so they can start the clinical trials if it is approved which was widely dependent on getting given a signed agreement from Otonomy.

As a result I reckon that Otonomy will proceed with this sometime soon since supposedly they view Frequency Therapeutics as a competitor. Though I think that Otonomy are quite busy doing the OTO-413 trial and also the OTO-104 trial which will hopefully finish phase 3 and get approved in the next few months.

 

[Billy_Shears]

Do you have insider information? Because if you do, the rest of us would love to hear it!

One does not need to have insider information to know that FX-322 will not be available in 2021. Frequency Therapeutics will present an end of study analytical report of Phase 2a in June, 2021. This report will also be presented to the FDA for review - just imagine the length of time that will take, despite fast track.

Even if a miraculous decision by the FDA has concurred that FX-322 has proven itself to render a cure for sensorineural hearing loss at best, it would take at least several months and up to a year to produce the pharmaceutical drug for market.

It's highly doubtful and yes, probably a 100% chance that you will not walk into an ENT physician's office and receive FX-322 as prescribed in the year 2021. I can only wish that I am so wrong.

 

[frpp]

Attached below is a link and snapshot to an article (Wall Street Journal) describing drug approval. There is a chance that the drug can go to market after phase 2.

Fast-Track Drug Approval, Designed for Emergencies, Is Now Routine

View attachment 41282

Making my day with this type of post. LET'S GOOOOOOO!!!

 

[frpp]

One does not need to have insider information to know that FX-322 will not be available in 2021. Frequency Therapeutics will present an end of study analytical report of Phase 2a in June, 2021. This report will also be presented to the FDA for review - just imagine the length of time that will take, despite fast track.

Even if a miraculous decision by the FDA has concurred that FX-322 has proven itself to render a cure for sensorineural hearing loss at best, it would take at least several months and up to a year to produce the pharmaceutical drug for market.

It's highly doubtful and yes, probably a 100% chance that you will not walk into an ENT physician's office and receive FX-322 as prescribed in the year 2021. I can only wish that I am so wrong.

Agreed. FDA review times are awful. FDA stands for:

Feet
Dragging
Association

 

[tommyd87]

One does not need to have insider information to know that FX-322 will not be available in 2021. Frequency Therapeutics will present an end of study analytical report of Phase 2a in June, 2021. This report will also be presented to the FDA for review - just imagine the length of time that will take, despite fast track.

Even if a miraculous decision by the FDA has concurred that FX-322 has proven itself to render a cure for sensorineural hearing loss at best, it would take at least several months and up to a year to produce the pharmaceutical drug for market.

It's highly doubtful and yes, probably a 100% chance that you will not walk into an ENT physician's office and receive FX-322 as prescribed in the year 2021. I can only wish that I am so wrong.

Approval will not be granted in 2021. Compassionate use might be, however. Having said that the question is how many ENTs would grant compassionate use requests. Right now, according to the FDA, it takes a fast tracked medicine/treatment less than 6 months to gain approval from the FDA.

 

[Street Novelist]

I guess I just can't envision a scenario where they release the results in May, showing it works, and then sit back and wait for the FDA to review the findings. Besides, I had the impression Frequency Therapeutics was working hand in hand with the FDA. So when they release the results in May, the FDA will already have reviewed them.

 

[tommyd87]

I guess I just can't envision a scenario where they release the results in May, showing it works, and then sit back and wait for the FDA to review the findings. Besides, I had the impression Frequency Therapeutics was working hand in hand with the FDA. So when they release the results in May, the FDA will already have reviewed them.

FDA won't review things until after the trial's totally completed. Currently they still have to review everything properly which means going through the same approvals process which for a fast tracked treatment/medicine takes up to 6 months.

 

[Diesel]

FDA won't review things until after the trial's totally completed. Currently they still have to review everything properly which means going through the same approvals process which for a fast tracked treatment/medicine takes up to 6 months.

@Street Novelist has a point; from the FDA website regarding FX-322's current Fast Track designation:

A drug that receives Fast Track designation is eligible for some or all of the following:

• More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
  
  
• More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
  
  
• Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
  
  
• Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

Rolling Review may be part of the incentive for the 90-day data release.

On Compassionate Use:

I know this is going to be an unpopular opinion; but I struggle to see from a business standpoint the value of putting any resources into enabling Compassionate Use in 2021/2022 if the drug may be in its pivotal phase. Why go through the work to start limited production with a drug manufacturer, price an experimental drug, deal with the individual paperwork, distribution, and deal with doctors. The price may be astronomical in low volumes for select use. Not to mention QUICKLY educating a workforce of ENTs on the drug and how it works, how to determine dosage, etc. Seems like a lot of resource and logistical problems.

 

[Street Novelist]

Great. So even if the results are what we expect, it could be years before we get access to the drug.

 

[Diesel]

Great. So even if the results are what we expect, it could be years before we get access to the drug.

In all of the tens of thousands of years of human existence, we've never been able to restore our own hearing naturally. Generations of people have come and gone with hearing loss and tinnitus. I'm willing to wait 2-3 more years if that means doing it right.

 

[Emgee]

In all of the tens of thousands of years of human existence, we've never been able to restore our own hearing naturally. Generations of people have come and gone with hearing loss and tinnitus. I'm willing to wait 2-3 more years if that means doing it right.

Hearing restoration is indeed a major breakthrough, but the fact remains that a drug exists right now that could potentially solve a good deal of our problems — yet we can't access it due to the existing bureaucratic system. The FDA approval process is ridiculously lengthy and stands in the way of us and FX-322. Some sufferers may not be in a position where they can wait 2-3 years. The system does not take those people into account, and it's tragic.

 

[Princebeyel]

Hearing restoration is indeed a major breakthrough, but the fact remains that a drug exists right now that could potentially solve a good deal of our problems — yet we can't access it due to the existing bureaucratic system. The FDA approval process is ridiculously lengthy and stands in the way of us and FX-322. Some sufferers may not be in a position where they can wait 2-3 years. The system does not take those people into account, and it's tragic.

I really don't feel I can wait that long. Even March is a long time for me.

 

[Christiaan]

In all of the tens of thousands of years of human existence, we've never been able to restore our own hearing naturally. Generations of people have come and gone with hearing loss and tinnitus. I'm willing to wait 2-3 more years if that means doing it right.

I really don't feel I can wait that long. Even March is a long time for me.

Me too. Let alone waiting 3 years. That would mean a death sentence for some of us.

 

[Born To Slay]

Hearing restoration is indeed a major breakthrough, but the fact remains that a drug exists right now that could potentially solve a good deal of our problems — yet we can't access it due to the existing bureaucratic system. The FDA approval process is ridiculously lengthy and stands in the way of us and FX-322. Some sufferers may not be in a position where they can wait 2-3 years. The system does not take those people into account, and it's tragic.

I hate to say it but it's not the system. It's Frequency Therapeutics. Compassionate use is built into the system for people that need it now but they haven't agreed to do that. I hate to be hard on them but it's true. We can't only blame the FDA.

 

[tommyd87]

@Street Novelist has a point; from the FDA website regarding FX-322's current Fast Track designation:

A drug that receives Fast Track designation is eligible for some or all of the following:

• More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
  
  
• More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
  
  
• Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
  
  
• Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

Rolling Review may be part of the incentive for the 90-day data release.

On Compassionate Use:

I know this is going to be an unpopular opinion; but I struggle to see from a business standpoint the value of putting any resources into enabling Compassionate Use in 2021/2022 if the drug may be in its pivotal phase. Why go through the work to start limited production with a drug manufacturer, price an experimental drug, deal with the individual paperwork, distribution, and deal with doctors. The price may be astronomical in low volumes for select use. Not to mention QUICKLY educating a workforce of ENTs on the drug and how it works, how to determine dosage, etc. Seems like a lot of resource and logistical problems.

Sorry I should have been clearer. I meant in regards to evaluating and assessing FX-322 after the completion of trials for market release.

Regarding compassionate use access:

I actually agree with you that from a trial, medicine and also a business standpoint that Frequency Therapeutics might not authorise compassionate use then because it might make little sense commercially to do it. It will therefore make much more sense for Frequency Therapeutics to take things slowly and get a completeness about FX-322.

My alternate position is however that it would make sense for Frequency Therapeutics to look at granting compassionate access for the following reasons.

> Granting compassionate (expanded) access means that Frequency Therapeutics can start making money off of FX-322 now through sales and also inflated price sales. Something says to me that there totally would be people that would pay 5 times the price to get it early.

> Frequency Therapeutics would be interested in training professionals how to use FX-322 now, as this would save further delays to the release of FX-322. This is because Frequency Therapeutics could actually commence training interested practices now on how to administer FX-322.

> Frequency Therapeutics can use the patients being treated through expanded access as actual examples to ENT clinics on the benefits of treating people with FX-322. This means that Frequency Therapeutics can demonstrate to practices the benefit of participation as an FX-322 treatment provider.

> Frequency Therapeutics has already got some providers participating in the trials who are versed in dosing FX-322 who would wholly be able to participate in offering expanded access to people.

Thus patients will not be the only ones who will benefit from the provision of FX-322 early through compassionate use. This is because Frequency Therapeutics can utilise this expanded access time to get doctors interested and also understanding how to dose people now before they have to do it in a much bigger and much more complex manner when FX-322 is hopefully released at full scale.

At this stage I think that it is possible that this could go either way. What we have heard and seen from Frequency Therapeutics is that they tend to be preparing and planning hopefully for FX-322 to get released, with the things they have done like preparing pricing and looking at how the distribution and treatment chain will work.

However consequently they could be getting on top of this stuff early so they can get it right for 2 years time when they theoretically could be finished with the pivotal phase by. I predict that we will know more in March 2021 maybe. My hunch is that depending on how the results are not only will we see Frequency Therapeutics look to submit their rolling review right away but also indicate other steps at that point in time too. Nevertheless I think that we will see Frequency Therapeutics attempt to do everything they can to get FX-322 released.

In all of the tens of thousands of years of human existence, we've never been able to restore our own hearing naturally. Generations of people have come and gone with hearing loss and tinnitus. I'm willing to wait 2-3 more years if that means doing it right.

I do definitely agree. If Frequency Therapeutics turns around and demonstrates that there will be benefit and further gains to patients by waiting till the end of phase 3 then I am in support of this. Better outcomes will probably be obtained by doing it right and I hope that we will widely see massive benefits come March/April when the 90 day release eventuates.

 

[Billy_Shears]

On Compassionate Use:

I know this is going to be an unpopular opinion; but I struggle to see from a business standpoint the value of putting any resources into enabling Compassionate Use in 2021/2022 if the drug may be in its pivotal phase. Why go through the work to start limited production with a drug manufacturer, price an experimental drug, deal with the individual paperwork, distribution, and deal with doctors. The price may be astronomical in low volumes for select use. Not to mention QUICKLY educating a workforce of ENTs on the drug and how it works, how to determine dosage, etc. Seems like a lot of resource and logistical problems.

From what I understand, many participants in the clinical trials have been United States combat veterans in the San Antonia, Texas area among other locations throughout the country. When we speak of compassionate use one can rest assured that U.S. military veterans up to age 85 will be the first to receive FX-322 and, as well, will be also serve as an educational resource for practicing ENT physicians - IF any compassionate use is offered at all.

It is probably wise not to get any hopes up on compassionate use for a pharmaceutical aimed at treating sensorineural hearing loss in the mild-to moderate range, a condition that hearing aids can often suffice.

Rather, hold out for the market that is surely to come no later than 2023-24 - we are actually fortunate it is this soon.

 

[Billy_Shears]

I guess I just can't envision a scenario where they release the results in May, showing it works, and then sit back and wait for the FDA to review the findings. Besides, I had the impression Frequency Therapeutics was working hand in hand with the FDA. So when they release the results in May, the FDA will already have reviewed them.

The Food and Drug Administration has literally hundreds of reviews going on with various pharmaceuticals, medical devices, cosmetics, food products, and more. Envision the FDA as being the planet Earth, Frequency Therapeutics would be a star, not the moon. This is why 2023 doesn't sound too bad after all.

 

[tommyd87]

I hate to say it but it's not the system. It's Frequency Therapeutics. Compassionate use is built into the system for people that need it now but they haven't agreed to do that. I hate to be hard on them but it's true. We can't only blame the FDA.

To be fair to Frequency Therapeutics, they have consistently been conservative in their approach to things and also have never made any announcements in relation to FX-322 that they have been unable to make as well either.

Essentially at the present point in time, it is almost impossible for Frequency Therapeutics to even contemplate offering compassionate use access as they would certainly get in trouble with various regulators if they stated that they were going to do this right now.

 

[Diesel]

From what I understand, many participants in the clinical trials have been United States combat veterans in the San Antonia, Texas area among other locations throughout the country. When we speak of compassionate use one can rest assured that U.S. military veterans up to age 85 will be the first to receive FX-322 and, as well, will be also serve as an educational resource for practicing ENT physicians - IF any compassionate use is offered at all.

It is probably wise not to get any hopes up on compassionate use for a pharmaceutical aimed at treating sensorineural hearing loss in the mild-to moderate range, a condition that hearing aids can often suffice.

Rather, hold out for the market that is surely to come no later than 2023-24 - we are actually fortunate it is this soon.

I could definitely see the US Military / VA gaining early access (if this is compassionate use) to the drug since the need is so great, the US Military is a massive purchaser, and Frequency Therapeutics did receive a grant from the military a few years ago.

 

[tommyd87]

From what I understand, many participants in the clinical trials have been United States combat veterans in the San Antonia, Texas area among other locations throughout the country. When we speak of compassionate use one can rest assured that U.S. military veterans up to age 85 will be the first to receive FX-322 and, as well, will be also serve as an educational resource for practicing ENT physicians - IF any compassionate use is offered at all.

It is probably wise not to get any hopes up on compassionate use for a pharmaceutical aimed at treating sensorineural hearing loss in the mild-to moderate range, a condition that hearing aids can often suffice.

Rather, hold out for the market that is surely to come no later than 2023-24 - we are actually fortunate it is this soon.

The issue is though that although hearing aids are a treatment, they are not the same kind of treatment. Those with hearing loss in the moderate-to-severe range would certainly want access to FX-322 sooner. I agree that 2023 is not far away; it is when FX-322 will likely get released and we are fortunate it is really not far away.

I am also wondering how you know it would only be veterans that would be eligible for compassionate use, if any is granted, out of interest?