Letter to the FDA (Dr. Janet Woodcock)

[FGG]

@FGG should send her personal letter as she pleases. Entirely her effort and her decision.

Tinnitus Hub and the community can send an additional separate and more formal letter. Though it's probably best to wait for promising results in regards to tinnitus (e.g. after FX-322 phase 2a) as this community letter would be in direct relation to tinnitus.

I think both angles are important. Personal more intimate angle and then the more general angle from a large community.

I agree that both are probably needed. Personal letters and a broader separate petition.

I don't think we need to wait until after phase 2 if we stress "if these drugs are effective." That's also one reason i don't like mentioning specific drugs and instead offering to open a dialogue with her. It can come off as premature if we start naming drugs at various very different study points. It is literally her job to be aware of all of these drugs. I just want her to be aware of the suffering.

I have sent a draft to a friend who has a friend who used to work for the FDA. I will be consulting with this friend to see what the best approach might be.

 

[Ben S]

I agree with everything you said. I want this affliction to be over as soon as possible, for myself and all of us. We need to work together and take action in order to get the ball rolling for these therapies. I am standing by and ready to help in any way that I can!

Also, my problem is mostly hearing loss. My clarity has taken quite the hit. So hopefully the restoration of HFs and UHFs essentially solves it. My fingers are crossed...

 

[FGG]

I really think we owe it to ourselves and the community to push full throttle at lobbying to label FX-322 "Breakthrough Therapy" if phase 2 shows the results we all hope for. I don't have years of patience in me; these last 7 months have felt like 7 years.

How is the letter going @FGG? Could you PM me her email perhaps? When I press email on the FDA website it doesn't register an appropriate recipient address.

Since the focus of the letter is on hearing disabilities, I think there is no harm in name-dropping NHPN-1010 and FX-322. Since the FDA has already fast-tracked FX-322 it would seem reasonable to pry as to whether conditional approval/Breakthrough Therapy labeling would be on the table if phase 2 goes well.

I truly think this drug holds more promise for treating tinnitus than it does hearing loss for a few reasons:

1. The participants who were administered the drug in phase 1 had more significant hearing loss (25-60dB @ 250Hz-8kHz) than do most tinnitus-sufferers. This would suggest:

• They probably had more support-cell depletion than people with little-to-no hearing loss.
• They likely experienced improvement in the untested frequencies above 8kHz where I believe the comparatively more intrusive/troubling tinnitus resides.

2. The drug better penetrates the base of the cochlea where HF- and UHF-associated HC's are located.

3. A gel would not discriminate against treating the untested notches of which I believe all tinnitus is composed. I believe the reason why tinnitus sufferers have difficulty matching the exact notch wherein the bulk of their tinnitus resides is because tinnitus is a composite of many untested regions of hearing loss. The bulk of my "loss" is at 16kHz, where there is a 25dB difference in pure tone audiometry between my R & L ear, so 16kHz is my dominant tone; however, when I try to sleep I can better hear the little nuances in the sound of my tinnitus—untested damage of HC's corresponding to 11kHz, 13,455kHz., etc. Indiscriminately sweeping all of these areas with the gel solution should correct the HC's that its surface area contacts.

Unfortunately, even if it works spectacularly for tinnitus, Frequency's trial isn't seeking a label for tinnitus. This means if it doesn't show any improvement in hearing, it can't be released without a new trial specifically for tinnitus. An experimental endpoint as i understand it is just valuable for off label use if it gets approved for the indication they are seeking (which is for hearing).

As such, it would still need to be shown effective for hearing loss. This is part of my push for surrogate end points if needed (e.g.. Word scores having more weight than audiograms if greater improvements shown).

Edit: this is why names dropping Hough's drug might be confusing since the trial, at this point, is for CI recipients.

 

[FGG]

I feel like maybe I need to explain this better and where the confusion might lie.

Frequency, Otonomy and Hough's drugs are not being primarily tested for tinnitus (well OTO-313 is, not OTO-413 but it's not regenerative and based on a user here's report I'm not super optimistic about that one).

Nether is Pipeline but, like Hough, they suspect it will be a good treatment. Frequency clearly thinks it will benefit tinnitus too based on their Q and A and the fact that suddenly they added tinnitus to their experimental arm.

None of these drugs are in an FDA trial for tinnitus, though. This means that it would be used off label, if effective. I very strongly suspect they will be very useful for tinnitus.

This is the point I think might have been lost, though:

We can't write to Dr. Woodcock and plead for her to approve a drug for an indication the drug is not in trials for. She has zero authority to change the entire FDA approval process for one drug. She can't decide that the tinnitus results of these drugs determine breakthrough status if the drug is not being tested for tinnitus unless it also is a breakthrough in terms of hearing. The reason she can't do that is because the IND was granted based on pre-clinical work for hearing, not tinnitus, and the endpoints and trial design were approved for it. Frequency knows this that's why they are just measuring one measure of tinnitus: TFI.

An example of what I mean: Rogaine started out as a blood pressure drug. If during clinical trials it didn't work for hypertension but grew hair (which they found out during trials it worked extremely well for), they couldn't then approve it for hair loss. BUT if it did work for blood pressure (which it did), they could approve it for hypertension and then people could use it off label for hair loss.

So asking the FDA to grant breakthrough status for tinnitus for drugs that are not being specifically tested primarily for tinnitus isn't the right approach imo. Instead, talking about how hearing loss and tinnitus are linked and then emphasizing that drugs that are shown to improve hearing can help us, too, is where i am going with this. Because no matter how much compassion she has for us, she can't re-write the rules but we can get her to understand many if not the vast majority of tinnitus sufferers could benefit from the same urgency she gives to hearing loss drugs.

Does this make sense?

 

[mrbrightside614]

Unfortunately, even if it works spectacularly for tinnitus, Frequency's trial isn't seeking a label for tinnitus. This means if it doesn't show any improvement in hearing, it can't be released without a new trial specifically for tinnitus. An experimental endpoint as i understand it is just valuable for off label use if it gets approved for the indication they are seeking (which is for hearing).

As such, it would still need to be shown effective for hearing loss. This is part of my push for surrogate end points if needed (e.g.. Word scores having more weight than audiograms if greater improvements shown).

Edit: this is why names dropping Hough's drug might be confusing since the trial, at this point, is for CI recipients.

You're right. I totally forgot about that. Fuck. Guess we just pray to god it has better efficacy on hearing than I suspect it will.

 

[Lucifer]

@FGG

You are right. It will be her job to know about these drugs. Keep us up to date.

 

[ajc]

@mrbrightside614

This is Janet Woodcock's email address:

Janet.Woodcock@fda.hhs.gov

I took this from a letter template The National Alliance of Advocates for Buprenorphine Treatment used when they tried to lobby her.

Email confirmed working.

 

[mrbrightside614]

@mrbrightside614

This is Janet Woodcock's email address:

Janet.Woodcock@fda.hhs.gov

I took this from a letter template The National Alliance of Advocates for Buprenorphine Treatment used when they tried to lobby her.

Email confirmed working.

Much love AJC. Plea to humanity incoming, whatever, I'll sell my dignity for a new ear.

 

[FGG]

Much love AJC. Plea to humanity incoming, whatever, I'll sell my dignity for a new ear.

Well, report back. I will probably wait on sending mine until I get the former FDA employee to read it and give me advice so I am sure she will get yours first in that case.

 

[FGG]

You're right. I totally forgot about that. Fuck. Guess we just pray to god it has better efficacy on hearing than I suspect it will.

It works well for hearing based on what we know.

One of the things I mentioned putting in my letter is stressing surrogate endpoints. This means word scores can have as much weight as an audiogram. This is all in the "hearing" realm (and needs to be) because that's the indication that the drug is being tested for.

 

[Lucifer]

Well, report back. I will probably wait on sending mine until I get the former FDA employee to read it and give me advice so I am sure she will get yours first in that case.

That's a good idea. Thank you for doing this.

 

[Barbara777]

I think we should all be sending letters to Janet Woodcock. If only one or two sends a letter, she won't even notice. But if hundreds of us send personal letters, she might pay attention.

 

[Lucifer]

I think we should all be sending letters to Janet Woodcock. If only one or two sends a letter, she won't even notice. But if hundreds of us send personal letters, she might pay attention.

I will definitely send a letter if it makes a difference. But will it matter if I'm not based in the US?

 

[Barbara777]

I will definitely send a letter if it makes a difference. But will it matter if I'm not based in the US?

I don't think country makes a difference. You don't need to say which country you come from in your letter.

 

[Lucifer]

I don't think country makes a difference. You don't need to say which country you come from in your letter.

What should I put in for the subject title in the email?

 

[all to gain]

I think we should all be sending letters to Janet Woodcock. If only one or two sends a letter, she won't even notice. But if hundreds of us send personal letters, she might pay attention.

If one letter is compelling enough, that's all it needs. It all depends on how she looks at things.

 

[Barbara777]

If one letter is compelling enough, that's all it needs. It all depends on how she looks at things.

Do you understand the number of emails she receives? FGG's letter is more likely to end up being unread than anything. More letters, more chance of her reading one of them. Actually for all we know she has a secretary previewing her emails...

What should I put in for the subject title in the email?

Something that catches her attention... "Janet, what can you do? I'm losing my mind."
But the subject title needs to come from your heart, decide for yourself.

 

[all to gain]

Do you understand the number of emails she receives? FGG's letter is more likely to end up being unread than anything. More letters, more chance of her reading one of them. Actually for all we know she has a secretary previewing her emails...

Something that catches her attention... "Janet, what can you do? I'm losing my mind."
But the subject title needs to come from your heart, decide for yourself.

She will almost certainly have a secretary, or two, checking her emails.

 

[HootOwl]

I am simply going to put this out there. I think that we should allow FGG to send her letter first and see if Janet responds. I think it's the least we can do given the amount of time and effort FGG has put into its drafting, and that it was her idea to begin with.

It's very compelling and well thought out and I seriously implore anyone who is thinking of sending an email to please hold off for at least a few weeks until we see if Dr. Woodcock responds. This could be our one chance to open a dialogue. We can always add or send more letters later but we can't take them back.

 

[FGG]

I am simply going to put this out there. I think that we should allow FGG to send her letter first and see if Janet responds. I think it's the least we can do given the amount of time and effort FGG has put into its drafting, and that it was her idea to begin with.

It's very compelling and well thought out and I seriously implore anyone who is thinking of sending an email to please hold off for at least a few weeks until we see if Dr. Woodcock responds. This could be our one chance to open a dialogue. We can always add or send more letters later but we can't take them back.

I truly don't care the least about the time and effort but I do wonder if a flood of letters asking to approve a drug with Breakthrough Therapy status *for* tinnitus that not in clinical trials for tinnitus will do much good. Because what can she do?

It would be equivalent of begging the FDA to have approved Trobalt faster so tinnitus users can use it off label. It is not how it works. On the other hand, Dr. Woodcock is insanely smart and can likely connect the dots at least. But asking for an action she can't legally do obviously won't work.

It is going to take a bit but I now plan to re-write my letter and send it through the former FDA friend that my friend has and again give my personal story and stress the surrogate hearing end points (something she can and should do to help us get the drug faster approval).

Let us know what y'all hear with this approach. It may take me a lot longer with the avenue I am now trying, anyway.

 

[FGG]

I don't think country makes a difference. You don't need to say which country you come from in your letter.

Her constituents are the American people, though. And her regulations follow US guidelines, law and regulations. It certainly won't *hurt* to send a letter but I encourage everyone to read about the FDA approval process first. It's quite different than Europe.

 

[mrbrightside614]

I still want @FGG on the lead with this.

I want to attach as many signatures as we can.

If it goes unread then maybe we send it out en masse.

I'm not sending anything first.

 

[FGG]

I still want @FGG on the lead with this.

I want to attach as many signatures as we can.

If it goes unread then maybe we send it out en masse.

I'm not sending anything first.

If anyone wants to send one first I strongly recommend not trying to plead for her to give Breakthrough Therapy status for the reason that people with tinnitus are suffering. Instead, argue for how hearing loss and tinnitus are linked and see if we can get her to use a *hearing* surrogate to approve a drug that will help more than just hearing patients in the process. So it gives her a reason to help *within the framework of what is possible in the FDA*.

If you aren't familiar with end point surrogates, I can give an example: to get a cancer drug approved faster you can look at median survival time even if other measures are not as rigorous (e.g.. Tumor size or biomarkers).

I don't think I can be the lead on a communal effort as I am realizing I am not very good at communicating my objectives!

So if y'all want to work in a joint effort, I am going to see if I can approach this through a different channel (that's all I am going to say for now). I'm leaving this thread for you guys to work on that effort together. Keep us posted!

 

[mrbrightside614]

If anyone wants to send one first I strongly recommend not trying to plead for her to give Breakthrough Therapy status for the reason that people with tinnitus are suffering. Instead, argue for how hearing loss and tinnitus are linked and see if we can get her to use a *hearing* surrogate to approve a drug that will help more than just hearing patients in the process. So it gives her a reason to help *within the framework of what is possible in the FDA*.

If you aren't familiar with end point surrogates, I can give an example: to get a cancer drug approved faster you can look at median survival time even if other measures are not as rigorous (e.g.. Tumor size or biomarkers).

I don't think I can be the lead on a communal effort as I am realizing I am not very good at communicating my objectives!

So if y'all want to work in a joint effort, I am going to see if I can approach this through a different channel (that's all I am going to say for now). I'm leaving this thread for you guys to work on that effort together. Keep us posted!

No, I totally get it. Please stay on track. Go with your gut, don't let our fingerprints muddy your words.

 

[Jack V]

I feel like maybe I need to explain this better and where the confusion might lie.

Frequency, Otonomy and Hough's drugs are not being primarily tested for tinnitus (well OTO-313 is, not OTO-413 but it's not regenerative and based on a user here's report I'm not super optimistic about that one).

Nether is Pipeline but, like Hough, they suspect it will be a good treatment. Frequency clearly thinks it will benefit tinnitus too based on their Q and A and the fact that suddenly they added tinnitus to their experimental arm.

None of these drugs are in an FDA trial for tinnitus, though. This means that it would be used off label, if effective. I very strongly suspect they will be very useful for tinnitus.

This is the point I think might have been lost, though:

We can't write to Dr. Woodcock and plead for her to approve a drug for an indication the drug is not in trials for. She has zero authority to change the entire FDA approval process for one drug. She can't decide that the tinnitus results of these drugs determine breakthrough status if the drug is not being tested for tinnitus unless it also is a breakthrough in terms of hearing. The reason she can't do that is because the IND was granted based on pre-clinical work for hearing, not tinnitus, and the endpoints and trial design were approved for it. Frequency knows this that's why they are just measuring one measure of tinnitus: TFI.

An example of what I mean: Rogaine started out as a blood pressure drug. If during clinical trials it didn't work for hypertension but grew hair (which they found out during trials it worked extremely well for), they couldn't then approve it for hair loss. BUT if it did work for blood pressure (which it did), they could approve it for hypertension and then people could use it off label for hair loss.

So asking the FDA to grant breakthrough status for tinnitus for drugs that are not being specifically tested primarily for tinnitus isn't the right approach imo. Instead, talking about how hearing loss and tinnitus are linked and then emphasizing that drugs that are shown to improve hearing can help us, too, is where i am going with this. Because no matter how much compassion she has for us, she can't re-write the rules but we can get her to understand many if not the vast majority of tinnitus sufferers could benefit from the same urgency she gives to hearing loss drugs.

Does this make sense?

GREAT letter. Thanks for doing this!

Two thoughts.

1) You could casually mention one or two drugs you're particularly excited about without making too big a deal out of it. For example, inserting FX-322 into your text:

"I know from reading op-ed pieces that you are personally very committed to FDA reform to make it work better for suffering patients. I ask that you consider us with debilitating hearing symptoms in these decisions, too. For the first time in history, regenerative medicine may help us. I'm particularly excited about the prospects of FX-322, and I'm sure you're familiar with many others as well. No matter which part of the cochlea is addressed: Outer hair cells, inner hair cells, cochlear synapse etc. I ask that, if any of these medications show efficacy in an important end point and are shown to be safe, I implore you and the FDA to help us get our lives back sooner.

Thank you so much for the work that you do. I know you fight for so many suffering people,..."

2) I would remove "Hi. Thank you for your time" from the opening and simply start with "I am a former veterinarian..."

Anyway, awesome letter!!!

Jack

 

[hans799]

Superbly written @FGG, thank you for doing this.

With all the recent activity here (the podcasts, the Lenire interviews, the attendance at and reporting back from conferences, this letter, etc), I feel that Tinnitus Talk/Tinnitus Hub is what the useless ATA/BTA should have been all along. Finally, a real advocate.

 

[Hazel]

With all the recent activity here (the podcasts, the Lenire interviews, the attendance at and reporting back from conferences, this letter, etc), I feel that Tinnitus Talk/Tinnitus Hub is what the useless ATA/BTA should have been all along. Finally, a real advocate.

Thank you! That's very kind and great to hear! It does feel like we're getting a lot done these days for just a small club of volunteers. Active members like yourself are what keep us going!

In this case though, we cannot take any credit, the letter to Dr. Woodcock was fully @FGG's own initiative. But we're always happy to facilitate any personal initiatives and draw attention to it.

We do by the way have some US political lobbying efforts coming up that are driven by Tinnitus Hub. It has to do with the NIDCD's strategic plan and an opportunity to give feedback there. You'll hear more about it very soon. @TuxedoCat, @mrbrightside614, @lcj, @Watasha and @HootOwl are working hard to prepare a coordinated effort here.

 

[lcj]

If anyone wants to send one first I strongly recommend not trying to plead for her to give Breakthrough Therapy status for the reason that people with tinnitus are suffering. Instead, argue for how hearing loss and tinnitus are linked and see if we can get her to use a *hearing* surrogate to approve a drug that will help more than just hearing patients in the process. So it gives her a reason to help *within the framework of what is possible in the FDA*.

If you aren't familiar with end point surrogates, I can give an example: to get a cancer drug approved faster you can look at median survival time even if other measures are not as rigorous (e.g.. Tumor size or biomarkers).

I think you said the reverse of what you meant to say. In oncology, median survival time/overall survival is the most critical endpoint that the FDA considers - other analysis are usually surrogate endpoints for survival. Sometimes survival can be expressed in a compound primary endpoint like progression free survival. Other endpoints like time to metastasis, time to radiographic progression, etc are usually secondary endpoints and endpoints like time to chronic opiate use may be secondary or tertiary endpoints, while biomarkers would usually only be considered as exploratory analysis (not qualifying under any of the endpoint analysis).

The reason surrogate endpoints are commonly used in oncology along with survival time is that for many populations and disease indications, people may not die fast enough in order for the study to collect enough data within a reasonable amount of time. But the FDA strongly prefers that the survival endpoint be co-primary, and it's very difficult to get approval with using surrogate endpoints alone.

You make an interesting point though regarding if there was a treatment for tinnitus/hearing loss what the measurable endpoints would be and which may be primary or surrogate.

 

[FGG]

I think you said the reverse of what you meant to say. In oncology, median survival time/overall survival is the most critical endpoint that the FDA considers - other analysis are usually surrogate endpoints for survival. Sometimes survival can be expressed in a compound primary endpoint like progression free survival. Other endpoints like time to metastasis, time to radiographic progression, etc are usually secondary endpoints and endpoints like time to chronic opiate use may be secondary or tertiary endpoints, while biomarkers would usually only be considered as exploratory analysis (not qualifying under any of the endpoint analysis).

The reason surrogate endpoints are commonly used in oncology along with survival time is that for many populations and disease indications, people may not die fast enough in order for the study to collect enough data within a reasonable amount of time. But the FDA strongly prefers that the survival endpoint be co-primary, and it's very difficult to get approval with using surrogate endpoints alone.

You make an interesting point though regarding if there was a treatment for tinnitus/hearing loss what the measurable endpoints would be and which may be primary or surrogate.

This is exactly why I need my friend's former FDA friend to read my letter first. I know the general concepts but if I want to use examples in other fields (I think it might be stronger to do that), I want to make sure they are the right ones that are applicable.

 

[Lucifer]

@FGG

Did you end up sending the letter in the end?