New University of Michigan Tinnitus Discovery — Signal Timing

[dj_newark]

510(K) clearance is around 90 days from what I'm reading.

That's if the device has been resubmitted as a 510(K). We hope that to be the case. I believe someone here on Tinnitus Talk did say that the device was resubmitted to the FDA once Lenire got the De Novo classification. However, I think that was conjecture and not based on fact. The only way we'll know for sure if the device was re-submitted as a 510(K) device is when Dr. Shore herself says it was. That was one of the questions I've asked in the QA session.

I've had this exchange with someone who claims to work in the medical device history and has a lot of experience with the FDA:

Ok, but when Lenire got the De Novo distinction from the FDA couldn't Shore and her team have re-submitted as a 510(k) device? If they were able to do that wouldn't that speed things up considerably?

Sure you can in theory, but it's a bit of a nuanced question/answer, and starting to verge into regulatory affairs. Substantial equivalence is meant when two devices are virtually the same in form, fit, and function which includes the method they achieve their intended use.

This is a complete nonsense analogy but to demonstrate the point, if you had a simple box and the box had a green button which turned a green light on when pressed using simple circuits and wires, that's materially different than a box which looks the same and also has a green light, but the method to achieve it's green light is through embedded software, LEDs, internet connectivity, etc. You could not claim equivalence between these devices despite having the same form and fit, because the function is completely different and the risks the later would not have been completely understood by FDA without further clinical trials.

I have not read the entirety of the clinical trials of both devices, but I do know what other users say about the method they are employing to treat tinnitus is entirely and completely different. Thus, it's on a De Novo pathway still.

That's his opinion, but it's one worth considering. I still believe that Lenire and the Auricle device may be "similar enough" from a regulatory point of view for the FDA to allow it to be considered as a 510(K) and not be on the De Novo pathway which would take a lot longer!

 

[IvanTheBad]

I have a pet theory: The reason Group 2 didn't see much improvement is because the auditory only stimulation they underwent in the sham part of the trial induced potentiation of the fusiform cells responsible for tinnitus. This likely left them less responsive to the treatment due to the short washout period. Dr. Lim and Dr. Shore have spoken about this possible effect with audio only stimulation in their research, and I would not be surprised if this turns out to be the reason most non-responders fell into Group 2 of Study 2.

Thoughts?

 

[Nick47]

The reason Group 2 didn't see much improvement is because the auditory only stimulation they underwent in the sham part of the trial induced potentiation of the fusiform cells

Then why did audio only reduce the loudness of the tinnitus?

 

[AfroSnowman]

That's his opinion, but it's one worth considering. I still believe that Lenire and the Auricle device may be "similar enough" from a regulatory point of view for the FDA to allow it to be considered as a 510(K) and not be on the De Novo pathway which would take a lot longer!

According to FDA website, "Under MDUFA IV, the FDA's goal is to make a decision about a De Novo request in 150 review days", so hopefully just a couple months longer.

 

[dj_newark]

According to FDA website, "Under MDUFA IV, the FDA's goal is to make a decision about a De Novo request in 150 review days", so hopefully just a couple months longer.

Yeah, in worst case scenario, let's hope it's just a few months away! There are a number of things that can influence a decision by the FDA:

The FDA considers a variety of factors when making a decision on a Class II DeNovo device, including the risk of the device, the intended use, the design and manufacturing, the clinical data, and the opinions of experts. The staffing levels at the FDA can also affect the decision-making process, as a lack of reviewers or reviewers who are not familiar with the specific type of device or the intended use can delay the review process. In addition to the staffing levels, other factors that can affect the decision-making process include the complexity of the device, the availability of alternative devices, and the public health need for the device.

 

[Abram]

I have it on good authority from a source at the UofM that they have not yet even begun the FDA application process. I cannot tell who my source is and you shouldn't trust anything a random username on the internet tells you, but maybe this Q&A will explain the delay more.

 

[Tomas80]

I have it on good authority from a source at the UofM that they have not yet even begun the FDA application process. I cannot tell who my source is and you shouldn't trust anything a random username on the internet tells you, but maybe this Q&A will explain the delay more.

If this is true, it is absolutely incomprehensible, like all the delays related to the device. I am extremely disappointed and distraught.

 

[dj_newark]

If this is true, it is absolutely incomprehensible, like all the delays related to the device. I am extremely disappointed and distraught.

As am I! I too am distraught. If there was presubmission to the FDA way back in 2017, why on earth would they be delaying submission now? Anything we say will be conjecture, but this makes the Q&A session with Dr. Shore that much more crucial! Someone I know of committed suicide last October. I can't imagine that they'd be playing with lives like this. There simply has to be a good reason for it!

Last April I got this email from Dr. Shore. She doesn't give any indication of what's happening with the FDA. But I can't imagine why she would say this if there has been no submission to the FDA:

Hello Tim,

Unfortunately, I do not have additional updates concerning the regulatory process with the FDA. Although I deeply understand the desire to have visibility on a possible therapeutic clearance, it is not permitted to publicly estimate, guess, or otherwise forecast when a currently non-cleared device or drug may become available. This can be considered to be marketing an unproven therapy and could therefore harm progress with the FDA as well as lead to sanctions for those offering such forecasts.

When we have any news that is appropriate to disseminate publicly, we most surely will. Until then, I appreciate your patience and understanding.

Warm regards,
Susan Shore

 

[Nick47]

I would be astounded and mortified if they haven't started a formal application.

All I could think is the trial participant number was not high enough or they queried the other arm that had placebo first.

I'm all for safety but we've just seen a useless so called vaccine appear out of thin air from manufacture to the market in 6 months. Remember this!

 

[ErikaS]

I have it on good authority from a source at the UofM that they have not yet even begun the FDA application process. I cannot tell who my source is and you shouldn't trust anything a random username on the internet tells you, but maybe this Q&A will explain the delay more.

If this is the truth, I am utterly disgusted. I am aware that we don't "deserve" to know every single detail, but many of us have beyond respected the level of confidentiality and "hush hush" that has surrounded this intervention and process. The least they could make clear is if it has officially been submitted to FDA or not. I thought she said something back in December about submission?

Before many who are suffering take this as fact and possibly make decisions they wouldn't have if it was false, is there ANY way @Hazel or @Markku could at least get confirmation on yes/no of an FDA submission and share with us as soon as possible?

Furthermore, IF it has not been submitted to FDA, I think a question we'd all agree in asking for the written interview is "Would Dr. Shore and Auricle Inc. consider a pathway of compassionate care use purchase if FDA submission is being delayed? In other words, could a patient, with comprehensive doctor/audiologist documentation of level of debilitation and need for treatment, purchase the device after signing of said documents confirming understanding it is pending FDA approval, and gain access to education for device use?"

Why not ask, right?

 

[ploughna]

The other big unknown is Auricle, the company. No mention of funding on any of the Angel investor databases, the only known employee is the CEO (and maybe one of the PhD students involved in the study whose LinkedIn profile lists him as Head of Engineering for Auricle). It takes a long time and a lot of money to develop this as a robust commercial product, then marketing, distribution, etc. I really hope I'm wrong but suspect this aspect is also a long way off.

As another great forum member (now deceased unfortunately) mentioned, it'd be so much better for all of us if these people could swallow their pride, get together with Neuromod (Lenire) under a licensing arrangement and get this to market in a fraction of the time - Neuromod has the funding, the R&D, the distribution channels, audiologist relationships, training resources, device design and manufacturing, logistics and supply chain, etc.

 

[Markku]

The least they could make clear is if it has officially been submitted to FDA or not. I thought she said something back in December about submission?

She has not made any announcements whether they have submitted to the FDA. Anyone emailing her will waste their and her time. She has stressed it many times that when they have news they can disseminate publicly, they will. She knows people want more transparency regarding the regulatory process. She would like to provide that, but as of now she can't. We have no choice but to respect that.

We are currently sorting out the questions to send her, and there will obviously be questions about the regulatory process, but I can't promise she can unveil more about it than she already has before. I think everyone should be prepared that it may continue to be a waiting game.

I think a question we'd all agree in asking for the written interview is "Would Dr. Shore and Auricle Inc. consider a pathway of compassionate care use purchase if FDA submission is being delayed? In other words, could a patient, with comprehensive doctor/audiologist documentation of level of debilitation and need for treatment, purchase the device after signing of said documents confirming understanding it is pending FDA approval, and gain access to education for device use?"

No matter what, this is a good question and we will include it.

 

[chinup]

I'm all for safety but we've just seen a useless so called vaccine appear out of thin air from manufacture to the market in 6 months. Remember this!

Worse than useless; it's the entire reason I'm on this website. But god forbid we try to fast track a treatment for the damage it has caused thousands of people like myself. What a total joke.

 

[Ed Fleck]

Dr. Shore's was a double blind, placebo controlled study - the gold standard. Neuromod's Lenire was not. Dr. Shore had NIH funding and a diverse study group. As Lenire was approved, there is no reason not to approve Auricle - a clearly superior device to Lenire and a superior study to Lenire.

 

[Dizzyhead888]

Dr. Shore's was a double blind, placebo controlled study - the gold standard. Neuromod's Lenire was not. Dr. Shore had NIH funding and a diverse study group. As Lenire was approved, there is no reason not to approve Auricle - a clearly superior device to Lenire and a superior study to Lenire.

Besides the shortcoming in Lenire's trials and besides the fact that Dr. Shore has been working on her device for over a decade, why does it seem to me that it is accepted intuitively on Tinnitus Talk that Dr. Shore's device is superior to Lenire?

 

[dj_newark]

Besides the shortcoming in Lenire's trials and besides the fact that Dr. Shore has been working on her device for over a decade, why does it seem to me that it is accepted intuitively on Tinnitus Talk that Dr. Shore's device is superior to Lenire?

Because Lenire is a habituation device. It does not lower tinnitus volume. Dr. Shore's device does. It reduced tinnitus volume by 50-75% in 12 weeks in her last human trial.

 

[UHPTS]

The other big unknown is Auricle, the company. No mention of funding on any of the Angel investor databases, the only known employee is the CEO (and maybe one of the PhD students involved in the study whose LinkedIn profile lists him as Head of Engineering for Auricle). It takes a long time and a lot of money to develop this as a robust commercial product, then marketing, distribution, etc. I really hope I'm wrong but suspect this aspect is also a long way off.

To me it all comes down to how they managed to get people from the two groups to know if they are receiving the treatment or not. I do firmly believe that people in both groups knew and the results were influenced by that. I do hope though that I'm wrong. However, there are many signs that something is not in order. One of them is what you mentioned.

They claim in their study that the threshold of the TENS signal was set so low that the participants couldn't feel it. Well if the participant doesn't feel it, then can the brain still sense it? Certainly we can feel the tingling of Lenire's tongue tip.

Also if they would set it to a certain threshold and this wouldn't be somewhat dynamic, then some variables still change even during few minutes. People's skin conductivity changes. The placement of electrodes can be slightly different in each treatment session. That makes me think that people in both groups could tell whether the TENS signal was present or not.

Maybe this could be converted to a question for Dr. Shore.

 

[Nick47]

To me it all comes down to how they managed to get people from the two groups to know if they are receiving the treatment or not. I do firmly believe that people in both groups knew and the results were influenced by that. I do hope though that I'm wrong. However, there are many signs that something is not in order. One of them is what you mentioned.

They claim in their study that the threshold of the TENS signal was set so low that the participants couldn't feel it. Well if the participant doesn't feel it, then can the brain still sense it? Certainly we can feel the tingling of Lenire's tongue tip.

Also if they would set it to a certain threshold and this wouldn't be somewhat dynamic, then some variables still change even during few minutes. People's skin conductivity changes. The placement of electrodes can be slightly different in each treatment session. That makes me think that people in both groups could tell whether the TENS signal was present or not.

Maybe this could be converted to a question for Dr. Shore.

I think blinding was always going to be tricky with bimodal devices. At least Dr. Shore tried to blind. Again the nature of the thread has changed due to one post. I can't see it being rejected, however the sheer scale of manufacture and distribution really needs a medium size team, especially at launch.

I would think there are considerable financial demands too.

I will say I ain't confident of a spring 2024 launch anymore.

 

[UKBloke]

This likely left them less responsive to the treatment due to the short washout period.

The short washout period of 6 weeks between treatment arms was discussed a few pages back. Entry criteria into the trial specified no tinnitus treatment for the prior 12 weeks upon trial commencement.

This suggests to me that the team consider 12 weeks to be a period of time where one would consider a candidate being treatment free. If that is the case then it does beg the question of whether or not halving the washout period between arms to 6 weeks led to some crossover of the effects.

I know this matter will go before Dr. Shore because I'm one of the ones who's put the question forward, however, until she confirms otherwise, I do wonder whether this was a weakness in the trial design.

 

[Ngo13]

Trying to bring in a little optimism here - in order to submit for FDA approval they should have their whole Design Control process completed, meaning marketing, distribution plans, etc. At least at my company that's what we do. Since they are a startup it might be a little different.

Point being, as soon as they get FDA approval they could be ready to launch extremely quickly. And if FDA approval is 6 months or less, we could still see the device being distributed by end of next year, even if they haven't submitted yet to the FDA. I certainly hope so anyway.

 

[F-u-T]

Does Dr. Shore own the rights to her research for this device as it was done at UofM? Would the UofM own any rights to this research or device? Could this be a cause of delay if it is true that FDA approval submission has not started? I'm not familiar how intellectual property works while conducted at public universities.

 

[awake 44]

If this is true, it is absolutely incomprehensible, like all the delays related to the device. I am extremely disappointed and distraught.

This is serious stuff. Questions like "Dr. Shore, when will the FDA approval be finished", or "Dr. Shore, when will the commercialization be completed" are pointless, as there are dozens of variables that are not under the control of Auricle.

However, we deserve clear information if they have already submitted their application to the FDA. It is simple, and does not require any promises from Dr. Shore's side. @Markku and @Hazel, please ask this one. It is absolutely crucial.

 

[Markku]

However, we deserve clear information if they have already submitted their application to the FDA. It is simple, and does not require any promises from Dr. Shore's side. @Markku and @Hazel, please ask this one. It is absolutely crucial.

We will ask, but you shouldn't expect that we can deliver that information. Based on our meeting with her, she won't be able to say yes or no.

 

[EDDTEKK]

Point being, as soon as they get FDA approval they could be ready to launch extremely quickly. And if FDA approval is 6 months or less, we could still see the device being distributed by end of next year, even if they haven't submitted yet to the FDA. I certainly hope so anyway.

Distribution by end of 2024? You think that's optimistic? I expected end of 2023 to be honest.

Come on Auricle, what's the problem? You have already spent two decades on this device. Do we really need to wait another decade to bring it to market... ugh.

 

[Jonno02]

I doubt they will really go into much about the FDA submission, it's a very sensitive thing.

We don't know if they have or haven't submitted, we just need to wait and see if anything comes from the Q&A.

If they haven't submitted, a partnership/licencing to an already established company that have the means and experience to bring this to fruition may be a potential route. An FDA submission isn't just "I did this study and here are my results." The most recent FDA submission I was involved in, about 6 weeks ago, was over 19,000 pages of documentation, reports, raw data, regulatory support files etc and took weeks and weeks of dozens of highly trained subject matter experts from a variety of backgrounds for a 'minor' change in an already approved device. I sincerely doubt UofM/Auricle have anywhere near these resources and/or experience.

It is a monumental undertaking and nothing to scoff at.

I've mentioned before that I deal with quite a few university programs like PhD students. The divide between academic science and industry science is quite vast. Universities do things that are a total no-no to us, even fairly basic things like their quality management systems (or lack of) are worlds apart from what industry requires, especially in the medical/pharma world. This comes as a shock to a lot of people when they transition from academia to industry and begin to get involved with regulatory bodies and can take some time to rectify before you are submission-ready. Not saying that's the case here at all, but if you need to go back through years of data and get it to a standard befitting of submission... it may take some time. A lot of people think that getting a publication is an achievement... that's absolutely nothing compared to getting regulatory body ready.

Again, all hearsay just now anyway, but just trying to shed a speck of light on how difficult a regulatory submission is, regardless of route but I'm just as much in the dark as everybody else.

 

[Nick47]

I doubt they will really go into much about the FDA submission, it's a very sensitive thing.

We don't know if they have or haven't submitted, we just need to wait and see if anything comes from the Q&A.

If they haven't submitted, a partnership/licencing to an already established company that have the means and experience to bring this to fruition may be a potential route. An FDA submission isn't just "I did this study and here are my results." The most recent FDA submission I was involved in, about 6 weeks ago, was over 19,000 pages of documentation, reports, raw data, regulatory support files etc and took weeks and weeks of dozens of highly trained subject matter experts from a variety of backgrounds for a 'minor' change in an already approved device. I sincerely doubt UofM/Auricle have anywhere near these resources and/or experience.

It is a monumental undertaking and nothing to scoff at.

I've mentioned before that I deal with quite a few university programs like PhD students. The divide between academic science and industry science is quite vast. Universities do things that are a total no-no to us, even fairly basic things like their quality management systems (or lack of) are worlds apart from what industry requires, especially in the medical/pharma world. This comes as a shock to a lot of people when they transition from academia to industry and begin to get involved with regulatory bodies and can take some time to rectify before you are submission-ready. Not saying that's the case here at all, but if you need to go back through years of data and get it to a standard befitting of submission... it may take some time. A lot of people think that getting a publication is an achievement... that's absolutely nothing compared to getting regulatory body ready.

Again, all hearsay just now anyway, but just trying to shed a speck of light on how difficult a regulatory submission is, regardless of route but I'm just as much in the dark as everybody else.

Good points made. It seems a bureaucracy of giant proportions. I expect CE approval is simpler.

Yes, I think Dr. Shore was hyper focused on the submission, when in reality it is a small bonus.

My only concern is if the FDA ask for 'more data' i.e. another study.

It may prove fruitful for them to pursue European and Australian markets first. It's what Neuromod did with Lenire. Lenire has been available in the UK for 2-3 years now, so all the hype in March 2023 about FDA approval felt weird to be honest. We had known for some time it didn't work.

 

[Jonno02]

Good points made. It seems a bureaucracy of giant proportions. I expect CE approval is simpler.

Yes, I think Dr. Shore was hyper focused on the submission, when in reality it is a small bonus.

My only concern is if the FDA ask for 'more data' i.e. another study.

It may prove fruitful for them to pursue European and Australian markets first. It's what Neuromod did with Lenire. Lenire has been available in the UK for 2-3 years now, so all the hype in March 2023 about FDA approval felt weird to be honest. We had known for some time it didn't work.

FDA is generally regarded as the most difficult, especially if you're not American. They have a bias towards approving American devices easier than international. Even with it being an American technology, if it gets approved in the US, other regulators generally follow.

I very much doubt they'll request any additional clinical studies. This isn't a pharmaceutical and the sample size of the recent study isn't out of the ordinary. By no means am I an expert in this particular field of device, but hopefully it's a case of getting their data submission-ready, rather than a larger issue.

 

[AfroSnowman]

FDA ask for 'more data' i.e. another study

I think that's what happened to Lenire which slowed down their USA roll out.

 

[Jonno02]

I think that's what happened to Lenire which slowed down their USA roll out.

Doesn't surprise me, they're a joke through and through. Probably submitted using their paid actor YouTube testimonials as proof.

 

[ErikaS]

I, and others I am sure, really appreciate the input form those who have any type of experience in the FDA submission process and share that with us. So thank you to those who have provided information and valid points.

I think what is so maddening and just wrong is the fact that society as a whole, or I should really say "the powers that be," have this ultimate control of what is of most importance to get to market and use, like @Nick47 said with the vaccines. Obviously the world needed a response to a pandemic, but because little old tinnitus isn't even a known condition to so many who don't suffer, yet it is the NUMBER ONE disability of the USA military followed by bilateral hearing loss at number 2. Yet NO ONE in "the powers that be" is in any rush or making it a priority to fund and push through a treatment or cure for those who literally risked their lives for this country, and a community that is full of individuals that would be normal functioning, working human beings if it weren't for this shit.

Therefore, more the reason to ask for the possibility of compassionate use avenues. And not just with this, pharmaceuticals as well.