Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator
- Thread starter jer
- Start date
Member
I want to pick your brain on something. I have been reading and posting stuff recently, and your comment kinda opened my eyes from my stupor.
Well, either one of or both companies are lying about their publishings.
Xenon Pharmaceuticals claims XEN1101 has no GABAergic properties based on these two links:
XEN1101, a Novel Modulator of Kv7.2/3 for the Treatment of Epilepsy
XEN1101: A Novel Potassium Channel Modulator for the Potential Treatment of Focal Epilepsy in Adults
And from my previous posts, Biohaven claims XEN1101 has GABA activity due to its side effects, but Xenon Pharmaceuticals outright denies them. Like you said, there isn't a source for their claims... Their PowerPoint presentation says [Biohaven Data on File (2022)]. Where is the data?
Biohaven also claimed BHV-7000 is the best in class Kv7.2/3 activator, but the recent data I posted under BHV-7000 thread suggests it is not as effective as XEN1101 (-15.2mV vs -42.5mV).
And there is not one study I could find, proving if these products affect GABA or not. It's he said, she said.
Messing around with GABA could be dangerous, it can lead to addictions and insomnia among other problems, upon quitting the drug. Since I have a GABA problem, I'm very afraid of the potential side effects the GABAergic properties of these drugs could cause.
Do you think we are being taken for a ride and will only know the true extend of the side effects when the drugs come out? Do you have any papers on how much they affect the GABA transmitters?
Key takeaways:
- Currently working towards an IND submission in Q1 2025.
- Following a successful submission, clinical testing can begin in 2025.
- Tinnitus is explicitly mentioned as a possible form of sensory hyperexcitability that can benefit from BSEN760 – but the focus appears to be on the treatment of chronic pain.
- In addition to point 3, they're hoping to improve on current standard-of-care treatments by eliminating various known side effects of said SOC.
With Tinnitus Week approaching, I'm not letting it go by with a whimper. It's a limited window of opportunity for us.
I have contacted the RNID who fund research and are much bigger than Tinnitus UK.
I have proposed we look at fundraising and designing a trial of XEN1101 for chronic tinnitus. It was an in-depth proposal with attached literature.
I have suggested reviewing the literature with Alan Palmer's group at Nottingham University.
We need these potassium channel modulators exposed as a dead duck or otherwise failure is still likely in chronic cases, in my opinion.
I have contacted the RNID who fund research and are much bigger than Tinnitus UK.
I have proposed we look at fundraising and designing a trial of XEN1101 for chronic tinnitus. It was an in-depth proposal with attached literature.
I have suggested reviewing the literature with Alan Palmer's group at Nottingham University.
We need these potassium channel modulators exposed as a dead duck or otherwise failure is still likely in chronic cases, in my opinion.
I'm pretty sure that XEN1101 will work to some degree for some people just like Retigabine, but it won't be the silver bullet that ends it all.
It will probably need to be taken for life or a very very long time. Just like how people with HPPD deal with antiepileptics.
Retigabine worked for chronic tinnitus cases, there are lots of people saying so on Tinnitus Talk, as you already know.
So, XEN1101 should not be a dead duck. It should do something, for some people, but to what extend, I can't say. And I don't know if tolerance would be an issue or not.
I'm more concerned about the potential side effects it could induce, such as Visual Snow Syndrome. Not one company working on these reformulated drugs addressing this is pretty suspicious to me.
We just need to work with the strongest Kv7 opener out there to see actual results. So far XEN1101 is the only option, which should be pretty similar in strength to RL-81, but as you know, it isn't the strongest.
Read my last post under the BHV-7000 thread. This part got my attention the most. And I also attached a schematic showing the voltage shifts.
We need a really really strong Kv7 opener and base our results on that. Hopefully XEN1101 also keeps those channels open long enough to induce plasticity changes.
Anyways, from my perspective, you have done God's work by contacting them. I hope they could get the thing and test it so that we would know if we are waiting for a dud or not.
The first hurdle is getting the RNID to bring the literature together to garner the interest of the researchers at the University. If they see merit and it's feasible to obtain and run a clinical trial, then it may be up to us to get a portion of the funding. There's 40,000 on here and 200,000 across various social media groups. Yes, the majority may not be active but with so many internet platforms, fundraising has never been more in reach. What it needs is strategy and focus.
Since getting tinnitus in 2015, I have never seen the community raise more than a couple of thousand pounds from some guy running a marathon. It starts with us, not others. [Further discussion here: Why Aren't You Donating Time or Money for Tinnitus Awareness / Research?]
There's no way to restore what's been lost inside the brain.
Mankind is still a hunter-gatherer society. Nobody is here to help us from the pureness of their heart. These positive tinnitus treatment news come out because companies want to attract investors and bump up their stock market value. I see most of the past promises by these companies as pump and dump schemes. There are still no effective treatments or cures.
We can only play around with the resulting hyperactivity. Potassium channel modulators did that and I expect XEN1101 to do that as well (unless the potassium channels are lost due to excitotoxicity). It is a band-aid solution. It is our best option. IMO.
They put it forward to the next year. Their original statement was:
Hi there - apologies for asking dumb questions as I'm not intimately familiar with the various research projects going on. When you say the potassium channel modulators being dead ducks - does that include the RNID funded research into HCN2 ion channel blockers (i.e. is that a dead end in your opinion)? If so, why?
Many thanks!
It's adjusted one quarter back, unfortunately. Yes, I think this is our only bet in the coming 12-15 months. Calming down hyperexcitability is the key to curing many diseases, epilepsy, pain, Alzheimer's, tinnitus... I do, despite the fact that no one talks about EMA approval in any of their publications. It's like there is no world or market outside of the US.
For Frequency Therapeutics, no, I don't like intratympatic injections. Damaging the eardrum is not good for people with tinnitus. The synapse regeneration thing is way too far back at the moment.
I've read my comment, and it doesn't come across that clear.
What I was trying to get across is we need them tested on tinnitus patients so we know if they work to put us out of our misery. All is speculation at the moment.
I don't buy the excuses we give pharmaceutical companies. For example, the line of "oh they need objective tests or they won't risk it." Bollocks to that! Depression, anxiety, schizophrenia etc. do not have objective tests and there are a plethora of treatments.
Part of me thinks they either know or suspect they will be dead ducks for tinnitus.
Xenon Pharmaceuticals are happy to trial it for MDD, guys!
The original primary endpoint was December 2025, so how can this be 12-15 months away? It would take 6 months for the approval, then manufacture and distribution. 28 months minimum, surely.
Yes, it all seems USA centric, considering 97% of the world population live outside the USA.
XEN1101 won't yield the results needed for it to be approved for tinnitus by the FDA. The results would be sporadic. There are too many moving parts and different pathologies involved in tinnitus. Nobody's going to test it specifically for tinnitus, it would take millions of dollars and lots of time to set up trials, only to risk it fail later on.
They are already testing it on "hyperexcitability." If they can get it out in the market for epilepsy, it would be prescribed off-label for tinnitus. No need to complicate their trials by testing it out on different ailments.
It's the same thing with Lamotrigine and Keppra. They are helpful for some visual snow syndrome/HPPD patients. Two different people could take a hit of marijuana and end up with HPPD. One could respond to Lamotrigine and keep their symptoms under control while on it, but the other might not respond to either of these drugs, even though they got HPPD the same way.
And the drug companies that came up with Keppra and Lamotrigine did not even do trials on visual snow syndrome. Other scientists did years down the road.
The above two paragraphs also apply to Retigabine.
By the way, only a small percent of people with visual snow syndrome/HPPD respond well to Lamotrigine.
They are willing to test XEN1101 for MDD, because it is a different market than hyperexcitability disorders and that market is HUGE and nobody's going to prescribe you an antiepileptic, like XEN1101, off-label for depression. They need to "prove" or lie to FDA that it works somewhat. For tinnitus, no need to risk anything at this stage, since many people are prescribed antiepileptics off-label for tinnitus already. XEN1101, no matter what the outcome of the trials are, would follow in their footsteps, and be prescribed off-label. Long story short, it was smart of them to test it for MDD, since it brings the use of this drug to an entirely different market, detached from hyperexcitability/epilepsy disorders, like tinnitus.
REMEMBER THAT THEY ARE NOT HERE TO HELP US, THEY ONLY WANT THEIR PRODUCTS TO BE SOLD.
The success of this treatment will depend on how much damage your auditory system and neurons sustained when you had your acoustic trauma, and over the years. Unless you fix the damage inside 1:1, these drugs can't cure anything for most people. But it will suppress the signals associated with tinnitus while you are on it/until you build tolerance based on the results with Retigabine. Maybe that could induce the necessary plastic changes for a group of patients and they will heal.
Such is the fate of using epilepsy drugs to treat hyperexcitability.
It's not 15 months away, but it's the closest so far. It's the only pill in Phase 3 where we are 100% sure that some people will benefit from it. Some people have achieved silence or near silence using Retigabine. Not a single pill in trials now or on the market available has ever been able to achieve that, not even in lab testing before Phase 1. Absolutely no miracle pills are coming up in the coming 10-15 years!
Sure, Retigabine was hit or miss. But even with 40-50% efficacy, this is going to help a lot of people.
We have no anecdotes of super responders for Dr. Shore's device. We don't know the impact on hyperacusis, or if there were people who perceived complete silence after the second trial.
Retigabine was tested on the most severe patient group (Tinnitus Talk). Many people improved, and we are aware of the placebo impact here. As far as I remember, Dr. Shore's device wasn't tested on people with hyperacusis or THIs over 60-70.
So XEN1101 is a wild guess, but Retigabine is the only medicine "proven" and tested on real-world tinnitus patients. Without the dangerous side effects and tolerance buildup, I'm sure many people would still be taking it today if it were available.
Retigabine was also proven to have horrible side effects like visual snow syndrome. Jumping out of the pan into the fire isn't that great.
Simply out of curiosity, were there any cases in which Retigabine made anyone's existing visual snow syndrome worse?
I was one of those who took Retigabine (Trobalt). I still have it available, but it is long expired.
I took it in "Aspirin Mode" when I was in really bad shape and had to function, meaning I had very loud tinnitus and an important appointment or something else. Trobalt reduced the tinnitus to a few levels lower for some hours.
Therefore, a comparable drug without the side effects would be great. Something that lowers tinnitus temporarily or perhaps, if taken for a longer time, drops tinnitus permanently.
Even if tinnitus cannot be lowered permanently, a drug that lowers or suppresses it for some hours (for example, during work hours) would be a life changer.
Did you not say you almost heard silence in some of your posts while you were on Trobalt? Like you were able to hear birds chirping again on your balcony or something. I read all the posts related to Trobalt so my memory might be messed up. I recall it did more than lower your tinnitus only a few levels.
I'm aware of a person who has had XEN1101 compounded or acquired it somehow. They have only been taking it recently but have had no impact so far, whereas they did respond to Retigabine, although sporadically. Obviously, I'm not naming them as it is their prerogative to tell or not. It is early days for them, though.
There are too many loose connections between XEN1101 and Retigabine, with Kv7.2/3 channels only directly implicated in animals for 'induction' or resilience to tinnitus, and that was Retigabine, NOT a selective drug like XEN1101.
There are too many loose connections between XEN1101 and Retigabine, with Kv7.2/3 channels only directly implicated in animals for 'induction' or resilience to tinnitus, and that was Retigabine, NOT a selective drug like XEN1101.
You forgot the story of people turning blue (irony).
Trobalt was not the poison some people would have you believe. Definitely a drug with too many side effects, I agree.
And XEN1101 will in all probability have side effects of the same nature, although attenuated.
No... this is my last hope. Please keep us updated with the results.
I remember Prof. Tzounopoulos also tested another selective compound, RL-81, on mice with success, so it isn't just Retigabine...
Maybe the compounded version of XEN1101 is defective?
I know that you need to use name-brand Keppra to treat HPPD; generic versions don't work at all. Maybe we are in a similar situation? Or maybe XEN1101 isn't as effective as Retigabine like you say...
I'm completely unfamiliar with anything that has to do with pharmacy, but I would like to echo your experience with name-brand medicines versus generic versions concerning efficacy.
Perhaps the compounded version is missing a certain step in the process. Also, note that @Nick47 mentions that said person only sporadically responded to Retigabine and has only recently started taking the compounded XEN1101.
Either way, interesting stuff. Thanks for sharing, @Nick47!
It depended on the level of tinnitus on that day. I would say that Trobalt reduced my tinnitus to a lower level.
My tinnitus varies between 10 (level of driving me crazy and being fully handicapped) and sometimes down to 5 (only one tone on the left side and more of a hissing). I had very few days in the past years where it was nearly silent. I cannot remember anymore whether it was on Trobalt or not.
But I can definitely say that Trobalt lowered my tinnitus. I took it maybe 10-15 times, and every time, it made a difference. It was not like a benzo which made me more relaxed, but the tone was the same.It was really a lower volume. Hence, I am looking forward to such a drug—perhaps in combination with Dr. Shores's device.
It should be sometime after the second half of 2026 at the earliest. It could be in 2027 or 2028. We can't say.
UHPTS
Member
- Jan 28, 2020
- 196
- Tinnitus Since
- 10/2019
- Cause of Tinnitus
- Taking drugs on penile fracture
What makes you think that XEN1101 will help tinnitus? They have been running clinical trials with hundreds of patients for years. Surely, some patients also have tinnitus. If those patients reported sudden improvement in tinnitus after taking XEN1101, wouldn't Xenon Pharmaceuticals seek to start a new trial for tinnitus? Treating tinnitus would be a gold mine for them.
Originally, I was going to type a long post going over some things, but I have done this a million times before. It's useless, being an armchair scientist. This wasn't me before this affliction hit me.
Instead, I will recommend a new alternative, but the people in power around here must take it seriously.
Most of the staff and community managers of these companies (Xenon Pharmaceuticals and Biohaven Pharmaceuticals) already know about the drug's potential in treating tinnitus. Plenty of people have already INDIVIDUALLY let them know about it everywhere.
I saw a post somewhere on the internet stating that Biohaven's community managers or other staff were open to conversations about it, but they were expecting it to come through a big organization like the American Tinnitus Association or something.
What needs to be done is clear, we need to get the ball rolling and ask them with the help of a credible, known organization, if their drugs work for tinnitus or not, if there are any success stories among the trial participants, if we should have any expectations for it, or set up a mini-trial of say ten people, if possible, instead of waiting for UP TO 5 YEARS and have a rude awakening ourselves if it doesn't do the job.
Is this possible, @Nick47?
I also want to add this. Let's say XEN1101 doesn't work. Then my question is, what mechanism made it possible for Retigabine to treat and sometimes give people permanent improvements in their tinnitus and hyperacusis? To my limited knowledge, no GABA drug or a calcium channel blocker does this; I still put my money on Kv7 channels being enough for tinnitus treatment, but say I am wrong and there is another mechanism I am not seeing in there, why is nobody trying to figure it out? If XEN1101 isn't it, why not reformulate Retigabine specifically for tinnitus while eliminating all the side effects?
In the pharmaceutical world, tinnitus doesn't seem to rhyme with "gold mine;" in my opinion, it's quite the opposite.
Very few conditions are more cheesy and despised than tinnitus.
Log in or register to get the full forum benefits!
Similar threads
