Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

[ErikaS]

I would think the best bet would be for someone in the US to contact the American Tinnitus Association. They could fund the initial pilot trials. So in effect they sponsor it. If it's efficacious, then it's a win for the pharma companies. If not, then it doesn't cost them either.

I live in the USA and would happily contact the ATA and wouldn't mind being a pest about it, but I would want to be direct and factual with the information I am saying wit the best evidence to back up what I am saying. I generally can speak on the matter on how these are two companies with Kv7 modulators coming down the pipeline, we know based on (insert papers/research/evidence here) that there could be a very good chance that these medications could significantly mitigate tinnitus and with the safety profiles, a pilot trial could be funded to possibly discover the benefits of these drugs for the millions of tinnitus sufferers?

Like I said, I am very able to call, email, ask to talk to higher up, etc. I just want to be prepared with the best evidence and words.

 

[Nick47]

but I would want to be direct and factual with the information I am saying wit the best evidence to back up what I am saying. I generally can speak on the matter on how these are two companies with Kv7 modulators coming down the pipeline, we know based on (insert papers/research/evidence here) that there could be a very good chance that these medications could significantly mitigate tinnitus and with the safety p

My thoughts are based on this:

1) The drugs exist.
2) Their safety profile is acceptable as they are in Phase 3 human trials.
3) Retigabine had efficacy in animal trials and human case studies.
4) Both Susan Shore, Thanos Tzounopoulos and several others have published papers on the potassium channels being involved in tinnitus.

That is the rationale and evidence deeming them suitable for exploration straight into a Phase 2, single centre trial. Phase 2, as no safety trial is required.

These pharmaceutical companies are not going to pay for a trial. The ATA have about $700,000 from the Texas Roadhouse funds. They would be the obvious sponsors and partners.

If the ATA was reluctant after consulting their scientific advisory committee, then we could petition them, using signatures from tinnitus patients. If we could get chief signatures from some researchers who would support this, all the better.

My concerns are unfortunately bureaucracy and conflicts of interest. On the ATA advisory board there are scientists and clinicians who are working on their own treatments who may not want to see an efficacious trial. That is sad, but I'm afraid a possibility.

Now that Tinnitus Talk is a registered charity in the US (Tinnitus Hub Inc), maybe we have more weight. I would be interested on how @Hazel and others who run the organization feel. I do think the community are going to have to take more of a leading role.

 

[Markku]

My thoughts are based on this:

1) The drugs exist.
2) Their safety profile is acceptable as they are in Phase 3 human trials.
3) Retigabine had efficacy in animal trials and human case studies.
4) Both Susan Shore, Thanos Tzounopoulos and several others have published papers on the potassium channels being involved in tinnitus.

That is the rationale and evidence deeming them suitable for exploration straight into a Phase 2, single centre trial. Phase 2, as no safety trial is required.

These pharmaceutical companies are not going to pay for a trial. The ATA have about $700,000 from the Texas Roadhouse funds. They would be the obvious sponsors and partners.

If the ATA was reluctant after consulting their scientific advisory committee, then we could petition them, using signatures from tinnitus patients. If we could get chief signatures from some researchers who would support this, all the better.

My concerns are unfortunately bureaucracy and conflicts of interest. On the ATA advisory board there are scientists and clinicians who are working on their own treatments who may not want to see an efficacious trial. That is sad, but I'm afraid a possibility.

Now that Tinnitus Talk is a registered charity in the US (Tinnitus Hub Inc), maybe we have more weight. I would be interested on how @Hazel and others who run the organization feel. I do think the community are going to have to take more of a leading role.

Hi @Nick47.

I like your idea, but I share some of the same concerns with you.

I usually don't want to publicly disparage any organization, but in this case I think it's prudent to explain why there's such an apparent lack of collaborative angle with the ATA.

It is not related to this idea of yours, but we have been trying to get a simple conference call set up with the ATA leaders, and it's impossible. It is as if they are purposefully ignoring our emails.

Just an example: @Hazel wanted to share some presentation slides of Jinsheng Zhang (ATA Chair of Board of Directors) from the ARO conference. He replied to her in early June, said he was traveling and promised to get back later. After multiple kind reminders, he never replied again, and it's now been many months.

Furthermore, we approached Jinsheng Zhang and a few other key ATA folks to request a conference call on a matter that we feel could benefit the whole tinnitus community, but we were 100% ignored, not even got a reply.

So at this point in time I feel ATA is very insulated and unwilling to collaborate with the tinnitus community at large, or at least with us.

We do have a few more tricks up our sleeves and hopefully we can steer this matter into a more fruitful direction. If we do end up being able to connect with them, we would be happy to put out feelers if they would be up for something like you suggested, but we'll see.

 

[Nick47]

Hi @Markku, thanks for picking this up. I, like many, have come to the conclusion that we have to do things for ourselves. There is a saying 'if you want the job done properly, do it yourself.'

I find it disheartening to hear that your attempts to engage with the ATA, who exist to advocate for us, has responded with radio silence.

They hold a fairly substantial pool of money, so they could fund clinical trials. Other than that, it would be a case of engaging with a pharmaceutical company and posing the idea of a trial. Discussions around trial design, recruitment, outcome measures, length of trial etc, and of course costings. It would then be up to us to raise the money. It sounds ambitious.

Biohaven have a compassionate use program for 'indications' that meet the medication use. It would be a way of access for severe sufferers, and fast track the process, rather than attempting to access it off-label in 2026.

But are we content with the advocacy and funding we get?

 

[ErikaS]

Hi @Nick47.

I like your idea, but I share some of the same concerns with you.

I usually don't want to publicly disparage any organization, but in this case I think it's prudent to explain why there's such an apparent lack of collaborative angle with the ATA.

It is not related to this idea of yours, but we have been trying to get a simple conference call set up with the ATA leaders, and it's impossible. It is as if they are purposefully ignoring our emails.

Just an example: @Hazel wanted to share some presentation slides of Jinsheng Zhang (ATA Chair of Board of Directors) from the ARO conference. He replied to her in early June, said he was traveling and promised to get back later. After multiple kind reminders, he never replied again, and it's now been many months.

Furthermore, we approached Jinsheng Zhang and a few other key ATA folks to request a conference call on a matter that we feel could benefit the whole tinnitus community, but we were 100% ignored, not even got a reply.

So at this point in time I feel ATA is very insulated and unwilling to collaborate with the tinnitus community at large, or at least with us.

We do have a few more tricks up our sleeves and hopefully we can steer this matter into a more fruitful direction. If we do end up being able to connect with them, we would be happy to put out feelers if they would be up for something like you suggested, but we'll see.

My gosh @Markku, this information enrages me and makes me want to vomit.

What is the point of the ATA and their existence if they don't even listen to, or even more so, collaborate with tinnitus sufferers?! Like where is their moral grounding and care for what they stand for?!

I agree with @Nick47, I learned a long time ago that relentless self advocacy may be the only thing that will get you an answer or a fair shot at something. So if that means a group of us from here starts to try to engage with one of these companies, I would gladly be on that "team".

@Nick47, has Biohaven commented on a list of conditions or indications that meet criteria for compassionate care use?

 

[Christiaan]

Biohaven have a compassionate use program for 'indications' that meet the medication use. It would be a way of access for severe sufferers, and fast track the process, rather than attempting to access it off-label in 2026.

Maybe it's worth contacting MyTomorrows? They help in facilitating compassionate use/expanded access between patients, doctors and pharmaceutical companies.

Link: https://mytomorrows.com/en

 

[DeanD]

It is sickening to read that ATA has turned its back on finding an actual cure for tinnitus because of inside corporate greed and self-interests. Unfortunately, this is a story told time and time again with large charitable organisations.

@Nick47 and @ErikaS are absolutely right of course. It will take people with a vested and sole interest in beating this thing with every fiber of their being to make change happen, like people behind Tinnitus Hub and the people on Tinnitus Talk.

Tinnitus Hub has already grown. It is known for having the largest community of tinnitus sufferers. It has an amazing 'foot-in-the-door' for gaining some attention in the online world. I'm not talking awareness weeks - those are mainly a waste of time - but I have spent years focusing on web building, online marketing, SEO, content generation and getting eyes on that content.

There are millions of searches per month on tinnitus and hyperacusis related questions mostly answered poorly by audiologist websites. I'd estimate Tinnitus Hub is receiving about 1,000 visitors a month (dropped by 50% in the past year), but if Tinnitus Hub provided content written to draw on those visitor questions to provide helpful meaningful advice, started gaining a different everyday audience - and display adverts along with affiliate links, there could be a very size-able amount of income generated for actual research.

With the right number of visitors looking for content, other things can happen. Visitors can be funneled through on to crowdfunding events or even a tinnitus online affiliate store (very easy to set up) to purchase things they normally would knowing that it costs them no more but that commission would be earned to support research to find a cure.

Tinnitus Talk also has a very strong email database which is a great kickstart to such a venture.

I've been involved in this industry for years and done this a number of times. I have looked at this a few times now and can just see a possible opportunity here.

This may not be the route the organisation intended to go but with money being the key factor here as to whether research can even get off the ground or not, it may be an option that could be considered.

I hope I am not overstepping the mark here but I am someone who sees an issue and wants to solve it, and am fed up of not being able to do anything of meaning.

I am happy to help, provide advice or even discuss some thoughts further with @Hazel and @Markku even if simply to share some thoughts on the idea.

 

[UKBloke]

Maybe a new thread for this line of discussion? There's a few points I'd like to add.

 

[Hazel]

It is sickening to read that ATA has turned its back on finding an actual cure for tinnitus because of inside corporate greed and self-interests. Unfortunately, this is a story told time and time again with large charitable organisations.

@Nick47 and @ErikaS are absolutely right of course. It will take people with a vested and sole interest in beating this thing with every fiber of their being to make change happen, like people behind Tinnitus Hub and the people on Tinnitus Talk.

Tinnitus Hub has already grown. It is known for having the largest community of tinnitus sufferers. It has an amazing 'foot-in-the-door' for gaining some attention in the online world. I'm not talking awareness weeks - those are mainly a waste of time - but I have spent years focusing on web building, online marketing, SEO, content generation and getting eyes on that content.

There are millions of searches per month on tinnitus and hyperacusis related questions mostly answered poorly by audiologist websites. I'd estimate Tinnitus Hub is receiving about 1,000 visitors a month (dropped by 50% in the past year), but if Tinnitus Hub provided content written to draw on those visitor questions to provide helpful meaningful advice, started gaining a different everyday audience - and display adverts along with affiliate links, there could be a very size-able amount of income generated for actual research.

With the right number of visitors looking for content, other things can happen. Visitors can be funneled through on to crowdfunding events or even a tinnitus online affiliate store (very easy to set up) to purchase things they normally would knowing that it costs them no more but that commission would be earned to support research to find a cure.

Tinnitus Talk also has a very strong email database which is a great kickstart to such a venture.

I've been involved in this industry for years and done this a number of times. I have looked at this a few times now and can just see a possible opportunity here.

This may not be the route the organisation intended to go but with money being the key factor here as to whether research can even get off the ground or not, it may be an option that could be considered.

I hope I am not overstepping the mark here but I am someone who sees an issue and wants to solve it, and am fed up of not being able to do anything of meaning.

I am happy to help, provide advice or even discuss some thoughts further with @Hazel and @Markku even if simply to share some thoughts on the idea.

Some excellent ideas there, Dean! In fact, you are describing a few things we were already planning for some time. We will reach out to you privately to discuss further

 

[Rhawnhurst]

I have had the same feeling about ATA. When I got tinnitus, I was excited that their new office was in walking distance from my house. Turned out that it was a one room office in an executive suite. Perhaps larger now.

I joined ATA. I get a very nice magazine every now and again. But I was always curious as to why 98% of the magazine was basically masking and biofeedback kind of stuff. I think we're all hoping that someone can get to the root cause. However, as pointed out, if that ever occurred, it could doom an industry and association.

I started a small monthly donation to Tinnitus Talk, to thank and encourage the work being done. Hopefully others can send a monthly amount, even if small. It adds up.

And hopefully we can encourage the powers that be to appropriate more money for basic research. What's amazing is that when someone does find a cure, it should become a multi billion $ enterprise in short order.

 

[Nick47]

This is an article on expanded access. People can contact Dr. James Shannon directly. Biohaven have expanded access programs.

MyTomorrows: an Interview with Dr. James Shannon

 

[ErikaS]

This is an article on expanded access. People can contact Dr. James Shannon directly. Biohaven have expanded access programs.

MyTomorrows: an Interview with Dr. James Shannon

Thanks for the info, @Nick47. How Biohaven and Xenon Pharmaceuticals are both missing the mark on a tinnitus trial is beyond me. There HAS to be someone among either group that is aware of the connection, the stalled tinnitus research with Professor Tzounopoulos, and the significant anecdotal and article evidence of using Retigabine off-label for tinnitus. It just amazes me how much our community continues to suffer due to so many missed marks or opportunities that are beyond blatant. Not to mention associations like ATA that sleep quite comfortably at night collecting their money while sufferers continue to suffer and they do nothing about it.

In the meantime, next time I meet with my neurologist I will do my absolute best to educate about Biohaven's Kv7 modulator, make him aware of their Expanded Access program, and will also set up a call with MyTomorrows. We literally have to do EVERYTHING our damn selves like you noted before and hope for a compassionate, listening, and agreeable ear.

 

[2noist]

There HAS to be someone among either group that is aware of the connection, the stalled tinnitus research with Professor Tzounopoulos, and the significant anecdotal and article evidence of using Retigabine off-label for tinnitus. It just amazes me how much our community continues to suffer due to so many missed marks or opportunities that are beyond blatant. Not to mention associations like ATA that sleep quite comfortably at night collecting their money while sufferers continue to suffer and they do nothing about it.

They are obviously aware of it but tinnitus is so hard to do clinical trials for with the lack of objective measurements. Every single pharmaceutical clinical trial has pretty much blamed their failure on that. No pharmaceutical company wants to take the risk anymore, even with the potential incredible payout.

Much easier to do epilepsy trials.

These companies also can't advertise it publicly if they think it might help tinnitus. They just hope it catches on with off-label usage, and then maybe if that seems successful, they are ready to do a trial for tinnitus to get that indication officially on the label.

Overall there must be a ton of epilepsy patients with tinnitus. If these drugs get approved and we don't start hearing their tinnitus is getting ameliorated, then we know it's a bust and we were just overly hopeful.

 

[ErikaS]

They are obviously aware of it but tinnitus is so hard to do clinical trials for with the lack of objective measurements. Every single pharmaceutical clinical trial has pretty much blamed their failure on that. No pharmaceutical company wants to take the risk anymore, even with the potential incredible payout.

Much easier to do epilepsy trials.

These companies also can't advertise it publicly if they think it might help tinnitus. They just hope it catches on with off-label usage, and then maybe if that seems successful, they are ready to do a trial for tinnitus to get that indication officially on the label.

Overall there must be a ton of epilepsy patients with tinnitus. If these drugs get approved and we don't start hearing their tinnitus is getting ameliorated, then we know it's a bust and we were just overly hopeful.

I agree, excuse my prior post that was composed with a lot of emotional and mental frustration.

I thought, after reading the interview with Dr. James Shannon that @Nick47 posted, that this statement could be a potential benefit to Biohaven and their early access use program with regard to tinnitus/hyperacusis/noxacusis:

Secondly, Dr. Shannon suggests companies should consider integrating EAPs into their clinical trial development strategy. EAPs present an important opportunity to collect Real-World Data (RWD).

So with regards to Biohaven, approve it for those whose doctor reaches out about a patient's life altering and debilitating tinnitus/hyperacusis/noxacusis, follow their progress, and use that real world data to their advantage moving forward with regards to possible future clinical trial.

 

[TuxedoCat]

They hold a fairly substantial pool of money, so they could fund clinical trials. Other than that, it would be a case of engaging with a pharmaceutical company and posing the idea of a trial. Discussions around trial design, recruitment, outcome measures, length of trial etc, and of course costings. It would then be up to us to raise the money. It sounds ambitious.

I just looked at ATA's website. The vast majority of board members are audiologists. There are 3 researchers - Dr. Zhang who is recruiting for his clinical trial for blast-induced tinnitus, Marc Fagelson who is an educator of audiologists and Phil Gander who, according to people we met at ARO, no longer does tinnitus research. Four of the seven people on the Scientific Advisory Committee are audiologists. That doesn't sound like a line up that would be open to funding a clinical trial of a pharmacologic agent.

More likely ATA is positioning itself to develop and promote better tinnitus management. I've seen ATA make passing reference to a portion of the money donated by Texas Roadhouse being used to further develop the phone hotline and the network of providers, most, if not all, of which would be audiologists. And, I suspect Texas Roadhouse had some say in the matter.

To the best of my knowledge ATA does not do clinical studies, they fund small seed grants as described on their website. If the Board of Directors and Texas Roadhouse intend to focus on the hotline and expanding the network of providers, there may not be much receptivity to a change of objectives for the research program right now.

So at this point in time I feel ATA is very insulated and unwilling to collaborate with the tinnitus community at large, or at least with us.

I agree with this, they seem to have set their own course and want to stick to it with no interruptions or diversions. And since they have board members who are tinnitus patients they have the patient view covered. I just find it frustrating that they do not even engage the wider tinnitus community - for heaven's sake tell us what is the vision for the ATA and the strategy for achieving the vision!

They are searching for a new CEO; let's hope they find one that is more engaging. Maybe we will be pleasantly surprised.

 

[haha ear go eeee]

So what's the point of ATA then? To sit on their asses collecting donations while the rest of us fight tooth and nail for money to put towards actual research? Christ, what a joke.

 

[gameover]

So what's the point of ATA then? To sit on their asses collecting donations while the rest of us fight tooth and nail for money to put towards actual research? Christ, what a joke.

Paychecks plus "feel good" about themselves. A bunch of unethical scammers like many non-profits.

 

[BTaylor12]

So what's the point of ATA then? To sit on their asses collecting donations while the rest of us fight tooth and nail for money to put towards actual research? Christ, what a joke.

Why would the ATA be interested in a cure?

That would mean the end of the ATA, lol.

 

[Jonno02]

Why would the ATA be interested in a cure?

That would mean the end of the ATA, lol.

Yep. It would mean useless grifters no longer collecting inflated salaries for doing sweet F all.

BTA and ATA are as useful as a chocolate teapot.

 

[Nick47]

I noticed in the literature from 2018, Xenon Pharmaceuticals said XEN1011 has possible indications for ALS and tinnitus.

 

[ErikaS]

I noticed in the literature from 2018, Xenon Pharmaceuticals said XEN1011 has possible indications for ALS and tinnitus.

Too bad they don't have an expanded access program. One could use that as a support statement for it.

 

[Nick47]

One could use that as a support statement for it.

It could be used as a support statement for Biohaven's expanded use.

 

[ErikaS]

It could be used as a support statement for Biohaven's expanded use.

That is true. Gotta throw everything at them that supports early access for our condition. Honestly, after reading about expanded access, it would be smart of either Biohaven or Xenon Pharmaceuticals to allow for tinnitus and use that real world data to their advantage to run a formal trial or not. I know a huge reason neither has gone down the path of a tinnitus trial is because we have no means of objectively measuring improvement, but there is also no objective means to measure improvement in bipolar and mood disorders unless I'm unaware of something? Anyway, it would be smart of them, in my opinion, to get real world tinnitus cases run their course and go from there.

 

[Nick47]

but there is also no objective means to measure improvement in bipolar and mood disorders unless I'm unaware of something

Good point.

 

[nrep]

People can contact Dr. James Shannon directly.

Where is his contact info?

 

[Nick47]

Xenon Pharmaceuticals are still recruiting for the Major Depressive Disorder clinical trial. There are sites in New York and Texas.

Anyone live near who could get in?

 

[ErikaS]

Xenon Pharmaceuticals are still recruiting for the Major Depressive Disorder clinical trial. There are sites in New York and Texas.

Anyone live near who could get in?

I just emailed the clinical trial contact for the New York location asking if I had to reside near there for treatment or if I could come there, do the enrollment process and get medication directions, and go home. Will see.

 

[ErikaS]

Shocker, another failed attempt.

1) You would need to live near the study sites due to frequent check-ins and things like MRI and EEG.

2) You can't be taking any other type of psych medication.

 

[Justwaitinchilin]

I tried to get in on the XEN1101 MDD trial as well. Same response. Never mentioned tinnitus, just leaned on MDD co-diagnosis.

 

[ErikaS]

I tried to get in on the XEN1101 MDD trial as well. Same response. Never mentioned tinnitus, just leaned on MDD co-diagnosis.

I will say the contact up in New York told me it's okay if you are on a benzo that is less than 2 mg a day, just cannot be on an antidepressant. I decided to forego as NY is not close to me by any means.