Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Is there a way to get emergency access going the FDA channel vs the compassionate use channel? My hyperacusis is ototoxic induced.

Not currently. Frequency has said they are not open to compassionate use at this time. That could change later, though.

Edit: I misunderstood your question. There is no other pre-approval channels other than compassionate use to get the drug, other than being part of a trial.

 

[Emgee]

If Phase 2a proves to be successful, and compassionate use/expanded access is opened up, I wonder what the requirements would be to obtain access.

For example, if someone has tinnitus but no detectable audiogram loss, would they be eligible? Or, would the need be granted based on hearing loss as that is the primary focus of the medicine? If tinnitus improvement is observed in Phase 2a, I hope the company allows access to tinnitus sufferers. This is all assuming expanded access is even opened up.

 

[Diesel]

If Phase 2a proves to be successful, and compassionate use/expanded access is opened up, I wonder what the requirements would be to obtain access.

For example, if someone has tinnitus but no detectable audiogram loss, would they be eligible? Or, would the need be granted based on hearing loss as that is the primary focus of the medicine? If tinnitus improvement is observed in Phase 2a, I hope the company allows access to tinnitus sufferers. This is all assuming expanded access is even opened up.

I have only limited knowledge of leveraging compassionate use protocols. However, if I am understanding it correctly, patients most likely to be applicable for compassionate use may not qualify for the trial, but should see a benefit.

So, with that known. Provided phase 2a data shows an improvement in tinnitus, but you don't have the hearing loss levels to qualify for the next phase; you might qualify for compassionate use.

However, the ENT applying on your behalf would need to be absolutely certain that your tinnitus would improve from the drug. So, it would almost have to be tone matched in the range that FX-322 is confirmed to treat.

 

[FGG]

But it's only a question of delivery right? I mean this drug regenerates to almost 100% in vitro?

I'm not sure the exact percentages but it was a very potent inducer of regeneration in vitro. It is reasonable to assume delivery is the roadblock if the results are less dramatic clinically. I have a feeling the ultra high frequency results will be extraordinary in the in vivo testing considering how dramatic the word scores changed.

 

[leledany]

I'm not sure the exact percentages but it was a very potent inducer of regeneration in vitro. It is reasonable to assume delivery is the roadblock if the results are less dramatic clinically. I have a feeling the ultra high frequency results will be extraordinary in the in vivo testing considering how dramatic the word scores changed.

What do you mean with the sentence "how dramatic the word scores changed"? From what I read it wasn't an extraordinary improvement. What am I missing?

 

[FGG]

What do you mean with the sentence "how dramatic the word scores changed"? From what I read it wasn't an extraordinary improvement. What am I missing?

Word scores doubled. Completely unprecedented.

 

[ASilverLight]

Personally I still think a combination of drugs is needed (e.g., this, synapse repair and meds like Dr. Thanos is working on) but anything can help reduce tinnitus until we have access to all of them.

I do believe even those with clear audiograms have hearing loss just because we can have a loss at any untested frequency.

Also hoping Europe gets this drug asap. I'll go anywhere as long as I can get it though.

 

[Diesel]

Word scores doubled. Completely unprecedented.

@leledany Clinically significant improvements in patients with word score deficiencies that received 1 dose of FX-322.

 

[aot]

For anyone doubtful or wondering wether or not FX-322 will help hyperacusis, just remember that Frequency Therapeutics follows Hyperacusis Research on Twitter. Food for thought.

I have a feeling today being July 4th, a few more people will join Tinnitus Talk over the next week. At least today, we're the closest we've ever been to a cure. And yet, so far away. I'm more than a year and a half with tinnitus so far, it's been one hell of a struggle... but I won't give up. I want to know who discovered the cure. Hopefully FX-322 helps at least a tiny bit over the next few years.

Yes, and that combined with possible hearing damage caused by COVID-19 (no reports of it as far as I know, but I wouldn't be surprised), the continued constant use of earbuds, and the loud protests against police, tinnitus and hyperacusis rates are due to skyrocket.

 

[Lucifer]

Personally I still think a combination of drugs is needed (e.g., this, synapse repair and meds like Dr. Thanos is working on) but anything can help reduce tinnitus until we have access to all of them.

I do believe even those with clear audiograms have hearing loss just because we can have a loss at any untested frequency.

Also hoping Europe gets this drug asap. I'll go anywhere as long as I can get it though.

Especially with hyperacusis patients their hearing tests all look normal but I reckon there is damage and if we can somehow restore OHCs, IHCs and synapses it should make the brain/ear reset the gain back to normal.

 

[Lucifer]

For anyone doubtful or wondering wether or not FX-322 will help hyperacusis, just remember that Frequency Therapeutics follows Hyperacusis Research on Twitter. Food for thought.

This has got to mean something. Maybe FX-322 does work with hyperacusis then.

 

[serendipity1996]

For anyone doubtful or wondering wether or not FX-322 will help hyperacusis, just remember that Frequency Therapeutics follows Hyperacusis Research on Twitter. Food for thought.

Good point - I've also noticed that Hyperacusis Research posts updates on Frequency's work on their Facebook page (e.g., the recent perilymph results etc) so I guess Bryan Pollard is keeping tabs on FX-322.

 

[Diesel]

This has got to mean something. Maybe FX-322 does work with hyperacusis then.

It means they're using Twitter's network effect to reach a wider audience. Of course, I'm hopeful it helps either way.

 

[Paulmanlike]

This is the ultimate question I am wondering from Frequency as discussed above. I had detectable hearing loss in one audiogram, then a normal audiogram in the other ones I did. I am on the assumption that I have hearing damage but it's subtle enough not to be detected in an audiogram but great enough to why I have chronic tinnitus.

Also, I'm right in assuming that I should be more focused on Otonomy's OTO-413 drug that targets hidden hearing loss through synapse repair rather than Frequency's FX-322 drug that is more targeted towards detectable hearing loss.

 

[Sloth]

Also hoping Europe gets this drug asap. I'll go anywhere as long as I can get it though.

I wonder when they'll start their trials in Europe. After all Astellas has the rights for the rest of the world so one might think that they're pressured to release it outside of the US just as fast.

Hopefully they don't start their trials after they fully release it in the US. I don't want to wait that long.
I'd also be totally down with entering their trials in Europe and I think they would take me as I have moderate to severe hearing loss at 8 kHz.

Does anyone know how the process works? Do they have to go through all phases in Europe again or do they just need one, pivotal study?

 

[egowisp]

How promising is this?

 

[Jurger]

If Phase 2a proves to be successful, and compassionate use/expanded access is opened up, I wonder what the requirements would be to obtain access.

For example, if someone has tinnitus but no detectable audiogram loss, would they be eligible? Or, would the need be granted based on hearing loss as that is the primary focus of the medicine? If tinnitus improvement is observed in Phase 2a, I hope the company allows access to tinnitus sufferers. This is all assuming expanded access is even opened up.

Can anyone here a name a drug for non life threatening disease where the company agreed to compassionate use before a Phase 3 trial?

If we would look at Otonomy for example, which has a Meniere's disease drug that's actually already completed a Phase 3 trial, they are still not allowing compassionate use. And unlike sensorineural hearing loss or tinnitus, Meniere's is a progressive disease. I want to be positive about the possibility of compassionate use, but what signal do we have that's within the realm of possibilities?

 

[Sloth]

How promising is this?

In my opinion it's very promising. Just look at the results of the phase 1/2 study (that was conducted with only 1 dose). They also tested it on live human cocheas ex vivo and had good results.
I think the only question left right now is not whether it works for hearing loss but whether it will actually help with tinnitus.
But since there are many reports of people's tinnitus improving by fixing hearing damage in one or another form I'm optimistic.
But we will know for sure once they release their phase 2a data.

I want to be positive about the possibility of compassionate use, but what signal do we have that's within the realm of possibilities?

I think it's highly unlikely that they will allow compassionate use while they are still recruiting. After that? I don't know.

 

[FGG]

Can anyone here a name a drug for non life threatening disease where the company agreed to compassionate use before a Phase 3 trial?

If we would look at Otonomy for example, which has a Meniere's disease drug that's actually already completed a Phase 3 trial, they are still not allowing compassionate use. And unlike sensorineural hearing loss or tinnitus, Meniere's is a progressive disease. I want to be positive about the possibility of compassionate use, but what signal do we have that's within the realm of possibilities?

It does seem like the companies themselves are the usual roadblock per this article:

https://www.statnews.com/2018/06/05/right-to-try-compassionate-use-pharma-compliance/

The article says the FDA themselves approve 95% of the requests.

It's hard to get a company to act against their own financial interests and ramp up production before release. If only we had a billionaire to front the costs.

 

[Emgee]

Can anyone here a name a drug for non life threatening disease where the company agreed to compassionate use before a Phase 3 trial?

If we would look at Otonomy for example, which has a Meniere's disease drug that's actually already completed a Phase 3 trial, they are still not allowing compassionate use. And unlike sensorineural hearing loss or tinnitus, Meniere's is a progressive disease. I want to be positive about the possibility of compassionate use, but what signal do we have that's within the realm of possibilities?

My example was all contingent on expanded access being opened up. Personally, I do not see that happening. It doesn't benefit the company.

 

[AtlasFainted]

It does seem like the companies themselves are the usual roadblock per this article:

https://www.statnews.com/2018/06/05/right-to-try-compassionate-use-pharma-compliance/

The article says the FDA themselves approve 95% of the requests.

It's hard to get a company to act against their own financial interests and ramp up production before release. If only we had a billionaire to front the costs.

This is why Right To Try isn't enough. We need provisional approval to let drugs actually hit the market earlier as opposed to a process that's riddled with red tape.

I do think this will happen via legislation and the FDA will also improve via reform, but probably not until at least a few years.

By that time FX-322 will already be out. But maybe these changes will help accelerate the release of OTO-413, Hough Pill, and other drugs.

 

[Jurger]

It does seem like the companies themselves are the usual roadblock per this article:

https://www.statnews.com/2018/06/05/right-to-try-compassionate-use-pharma-compliance/

The article says the FDA themselves approve 95% of the requests.

It's hard to get a company to act against their own financial interests and ramp up production before release. If only we had a billionaire to front the costs.

If a patient is able to pay for the drug him/herself, the direct financial consequences should be limited. The big roadblock of course is that every patient that gets the drug via compassionate use, is one less patient that won't participate in a trial. And of course any adverse effects that might arise, although with FX-322 that doesn't seem to be likely.

 

[Diesel]

My example was all contingent on expanded access being opened up. Personally, I do not see that happening. It doesn't benefit the company.

The preferable route is Breakthrough Therapy status, which imo, if the Phase 2A looks anything like the Phase 1/2, it is highly likely. And a Phase 3 that is a year in duration.

If they do allow expanded access, it would absolutely have to be in cases where a patient does not meet the acceptance criteria of the Phase 3. So, if you have mild - no hearing loss on the standard audiogram, solid word score, but raging tinnitus in the high frequencies, for example. Or, for those of you that already applied to the Phase 2A, but were turned away, you may be applicable for expanded use.

Also, let's not forget about the Promising Pathway Act. A provisional approval for a drug like FX-322 may provide for early manufacturing and sale of the drug. Based on the wording of the current bill, provisional approval does make financial sense for the drug manufacturer. It allows them to produce a "promising" drug as long as they continue the final phases in parallel.

However, it will probably end up similar to expanded use imho.

 

[AtlasFainted]

If a patient is able to pay for the drug him/herself, the direct financial consequences should be limited. The big roadblock of course is that every patient that gets the drug via compassionate use, is one less patient that won't participate in a trial. And of course any adverse effects that might arise, although with FX-322 that doesn't seem to be likely.

There's actually legislation that says the FDA can't take what happens with Right To Try cases into consideration when considering a drug for approval - only the cases in actual clinical trials.

Also one of the requirements for compassionate use is that you don't qualify for a trial. I suppose maybe you could find a way around this (say that you can't travel?), but personally I feel like the biggest roadblock is the initial investment to ramp up production, and that Frequency would have to devote resources away from clinical trials in order to do so, and also handle all the Right To Try paperwork coming in (there would be a TON).

Not so much the case if the drug were simply given blanket provisional approval. Phase 1 trials already showed it to be at least relatively safe. Release the drug as "phase 1 safety approved" while you also push through the more nuanced trials.

Or even do the same thing, but for Phase 2a - dosing would be figured out better by then. Then healthcare providers can buy it in bulk, with much less time & resources being spent on Frequency's end.

 

[FGG]

If a patient is able to pay for the drug him/herself, the direct financial consequences should be limited. The big roadblock of course is that every patient that gets the drug via compassionate use, is one less patient that won't participate in a trial. And of course any adverse effects that might arise, although with FX-322 that doesn't seem to be likely.

It costs many millions to build a production facility to produce large quantities of drug. It's a big up front cost that goes beyond cost per drug that, especially with a publicly traded company, the stock holders would have to front until enough patients were dosed with compassionate use.

I suspect this is one of the additional reasons cancer drugs (which can run a million dollars plus per treatment course in some cases) get approved by companies for compassionate use often.

 

[Emgee]

If a patient is able to pay for the drug him/herself, the direct financial consequences should be limited. The big roadblock of course is that every patient that gets the drug via compassionate use, is one less patient that won't participate in a trial. And of course any adverse effects that might arise, although with FX-322 that doesn't seem to be likely.

Frequency could open up compassionate use after recruitment for Phase 2b or 3 (final phase) is complete. That way, they get their trial participants and people who fail to meet trial criteria can receive access.

 

[Emgee]

The preferable route is Breakthrough Therapy status, which imo, if the Phase 2A looks anything like the Phase 1/2, it is highly likely. And a Phase 3 that is a year in duration.

If they do allow expanded access, it would absolutely have to be in cases where a patient does not meet the acceptance criteria of the Phase 3. So, if you have mild - no hearing loss on the standard audiogram, solid word score, but raging tinnitus in the high frequencies, for example. Or, for those of you that already applied to the Phase 2A, but were turned away, you may be applicable for expanded use.

Also, let's not forget about the Promising Pathway Act. A provisional approval for a drug like FX-322 may provide for early manufacturing and sale of the drug. Based on the wording of the current bill, provisional approval does make financial sense for the drug manufacturer. It allows them to produce a "promising" drug as long as they continue the final phases in parallel.

However, it will probably end up similar to expanded use imho.

I hope I'm wrong, but I just don't see them opening up expanded access. I agree that the Breakthrough Therapy designation is much more likely. If it's not designated, Frequency is going to allocate all of their resources into study design and implementation for the final phase. I'm sure they don't want to have to deal with compassionate use requests at the same time.

When could we expect it to hit market if Breakthrough Therapy status is granted?

 

[Diesel]

There's actually legislation that says the FDA can't take what happens with Right To Try cases into consideration when considering a drug for approval - only the cases in actual clinical trials.

Also one of the requirements for compassionate use is that you don't qualify for a trial. I suppose maybe you could find a way around this (say that you can't travel?), but personally I feel like the biggest roadblock is the initial investment to ramp up production, and that Frequency would have to devote resources away from clinical trials in order to do so, and also handle all the Right To Try paperwork coming in (there would be a TON).

Not so much the case if the drug were simply given blanket provisional approval. Phase 1 trials already showed it to be at least relatively safe. Release the drug as "phase 1 safety approved" while you also push through the more nuanced trials.

Or even do the same thing, but for Phase 2a - dosing would be figured out better by then. Then healthcare providers can buy it in bulk, with much less time & resources being spent on Frequency's end.

It costs many millions to build a production facility to produce large quantities of drug. It's a big up front cost that goes beyond cost per drug that, especially with a publicly traded company, the stock holders would have to front until enough patients were dosed with compassionate use.

I suspect this is one of the additional reasons cancer drugs (which can run a million dollars plus per treatment course in some cases) get approved by companies for compassionate use often.

Just to be clear on this. Frequency is not planning to directly manufacture FX-322 with their own facility. They have said so in their 10-K. They retain the rights to distribute/commercialize in the US. They are planning to contract production of the drug with Astellas and/or another 3rd-party "FDA-compliant manufacturer."

The way I read the 10-K, Astellas will probably manufacture the drug, and Frequency will slap their label on it and get the commercial gains within the US. This is an ideal situation; Astellas brings the manufacturing expertise / assets, Frequency gets the cashflow.

The good news for us is the ramp-up time required to stockpile the drug will be short; and Astellas may be able to start manufacturing prior to FDA approval. Astellas also has established distribution to get the drug to providers.

 

[Emgee]

I really hope there's an anecdote regarding reactive tinnitus in the Tinnitus Functional Index data when Phase 2a results are announced.

Even if it doesn't help fix reactive tinnitus, I'm still rooting for all of you. I might just be a lost cause.

 

[tommyd87]

My example was all contingent on expanded access being opened up. Personally, I do not see that happening. It doesn't benefit the company.

It won't benefit Frequency. It has been noted that Astellas will make a payment to Frequency if they complete 2b so there is no way it won't be done because they will want and need the money.

Furthermore I don't see them allowing compassionate usage either as they will want to produce the best quality medicine first before this is even considered.