Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

Hi @DocTors_94, did you email them and did you get any reply?

 

Hi @Freerunner. I emailed them twice on 21st of January. No reply. Seems the world doesn't care about us the extreme sufferers. I'm done seeing how unempathetic people are. I would give my kidneys to have those meds now...

 

Xenon Pharmaceuticals Reports 2021 Financial Results and Provides Corporate Update

Some interesting updates.

Phase 2 for depression to start in H1 2022.

Reiterates plans for Phase 3 for epilepsy in 2022.

This is the great hope for us tinnitus sufferers. All in my opinion of course but I’m first in line for this drug if possible.

The big thing for the Tinnitus Talk members is that many of us would qualify for this depression trial. It would be amazing if some of our members could get on the trial.

First time we could test a Retigabine reformulation.

Anyone that can find info on trial locations when published, please share.

 

Below is a link to the thread where Retigabine (Trobalt) users posted their experiences. This is for anyone new and doesn’t realise the potential that XEN-1101 has.

Also consider XEN1101:

1. Is many times more potent at a far less of a dose than Trobalt.
2. Is more selective focusing on the correct potassium channels.
3. Has a minimal side effect profile vs placebo and has exhibited NONE of the serious side effects of Trobalt.
4. Works on calming hyperactive neuronal activity by regulating the potassium channels. ‘Putting the brakes on’ to simplify it.
5. The company are optimistic regarding depression. The content in the link above is very positive on the drug. The Mt. Sinai trial must be going well if the company is progressing to a company sponsored Phase 2.

Here is the link to experiences as regards tinnitus with a less potent drug formulation and also a far greater side effect profile, Retigabine (Trobalt):

Retigabine (Trobalt, Potiga) — User Experiences

I genuinely can’t understand why this isn’t being hyped on the site.

 

That's pretty simple. The drug is being tested for depression and epilepsy, not tinnitus. As far as I know the positive effects from Trobalt are anecdotal.

I'm following this one closely though, since Professor Thanos is working on something similar which he believes will help us.

 

I’m pretty sure some users in the past had bad results that negatively impacted their quality of life. It was kinda rough to see/hear about. I think I know one or two people in particular who suffered tremendously after taking Retigabine/Trobalt. Over the past few years we’ve lost quite a few members and sometimes drugs like this reminds people of them.

It seems great but that’s also a reason why I have a hard time checking some of the trials.

 

That is a great point. I apologise if it brings up bad memories. Trobalt was a dirty drug but it did improve tinnitus despite horrid side effects. I think the new formulation is far less dangerous, by multiples, but I appreciate what you are saying. Insensitive of me, particularly as someone who themselves suffers with 'suicidal ideation' due to tinnitus.

Let us hope Retigabine (reformulated) ends up saving more lives in the future. I am optimistic it might.

 

I don't know if anyone has put this document on Tinnitus Talk, but Xenon has published a pharmacokinetic report on XEN-496 some time ago. The results are quite interesting (and comparable in many respects to Retigabine/Trobalt/Potiga) and has a favourable side effects profile.

Conclusions:

• In this Phase 1 PK and safety study in healthy adult volunteers, XEN496 was generally safe and well-tolerated.
• Overall, XEN496’s safety profile was comparable to that of Potiga.
• XEN496 performed as expected for an immediate-release pediatric dosage form.
• Administration of a single 400 mg dose of XEN496 in the fed state slightly reduced and delayed ezogabine’s peak plasma concentration, but did not affect its extent of systemic exposure, compared to the fasted state.
• Although food slightly delayed the time to reach NAMR (ezogabine metabolite) peak plasma concentration, total systemic exposure of NAMR was not affected.
• The biopharmaceutical performance of XEN496 was comparable to that of Potiga, suggesting that no formulation-related dose adjustments are indicated for future clinical studies.

 

@Padraigh Griffin, I believe once people see or hear effects for people with tinnitus then they’ll be more excited for this one. People really thought Trobalt was the cure a few years ago so it’s just a super sore spot. I’m kinda against bashing anything on the research forum because you never know how much people attach a drug/possibility to their happiness/will to live.

You didn’t come off as insensitive at all. A lot of people just don’t know or have never witnessed how the failure of a drug can effect people on this platform.

 

What is more relevant is that the data from Phase 2B safety study for XEN1101 indicated that of those in the treatment group, 68.6% experienced adverse effects on a 20 mg dosage.

BUT:

In the placebo group 62.3% experienced adverse effects.

Draw your own conclusions from that.

 

I have been reading past presentations and XEN1101 is 16 times more potent than Retigabine and safety study data is, as aforementioned, very favourable. Zero pigmentation side effects plus 2 urinary retention (about 1% of cohort) that were sorted easily with dose reduction.

Look, I know it’s not even been trialled for tinnitus but the Dept of Defense are funding Professor ‘can’t spell his name’ at Pittsburgh University with $2M grants. They are still pre-clinical.

Here we have a far nearer the market company with $545M cash and a good reformulation entering Phase 3.

I’m focused on this one big time. It would be epic to get on the depression Phase 2 trials but I doubt there will be any in my country. Maybe UK? Certainly US.

 

@Padraigh Griffin, I am optimistic about XEN1101 too and would like to try it. I think it’s definitely one of the best looking prospects in the pipeline for tinnitus.

One thing that I saw on the clinical trial for their depressive disorder study is that MRIs are going to be part of it (to image the brain, I think). Not sure if people with tinnitus will want to take part in that if I am interpreting it right. Maybe I’m wrong.

I wonder why they aren’t doing any clinical trials for tinnitus?

 

Clinical trials cost millions.

 

I don't know. It's strange. There must be heaps of $$ to be made if it works. Maybe there is a reulctance because there is no drug which works for tinnitus despite many attempts and they have drawn the conclusion that as a consequence this one probably wont work either?

Maybe people with depression are easier to manipulate than people with tinnitus (i.e. we are a tougher bunch and won't accept a treatment that doesn't work!).

Or maybe tinnitus is not considered a serious enough condition to warrant investment?

Meanwhile there are many many drugs that treat depression.

 

I presume that getting it on the market for its primary treatment, which is focal epilepsy, would be great.

Then depression is the big big market. If it shows efficacy for this, it could disrupt the huge SSRI market.

In essence a ‘depression’ trial is one for tinnitus too as most people struggling with tinnitus and are willing to take this pill would also have some form of depression.

It can be prescribed off-label for tinnitus easily but it need not technically be off label as tinnitus distress = depression of some sort.

 

Been digging further into this. Just a point of note regarding depression.

This presentation is solely about XEN1101's proposed efficacy for depression with data from Retigabine 300mg studies included:

https://www.xenon-pharma.com/wp-content/uploads/2021/02/RS_ASENT2021_Kv7Depression_FINALiii.pdf

I know a lot of tinnitus sufferers have associated depression so it may be of interest, especially as SSRIs are known to cause or worsen tinnitus.

It is interesting to see that depression burden in epilepsy is comparable to the burden in severe tinnitus patients.

It looks very promising. We should have news from the Mt. Sinai trial soon.

Also here is a detailed poster with more detail on side effects from Phase 2B X-TOLE STUDY for those who are worried about the Trobalt severe side effects. There appears to be little need to worry:

https://www.xenon-pharma.com/wp-con...022_-XTOLE-Topeline_French_Poster_2-21-22.pdf

 

The market is very excited about this drug. Hyperexcitable even. Lots of news in the next three months.



I'm first in line for this when it comes. I really believe this drug will help us tinnitus sufferers.

 

We know. You post everyday about it.

 

I'm starting to think he invested quite a bit in the company

 

@Nobody19, nope, no investments in Xenon but would be tempted, but to be completely honest my track record in Biotechs is shite from an investment POV. I lost a lot in FREQ for example.

Guess I'm just excited about this treatment and see it as the most probable near term solution to my plus others suffering.

This thread is dead.

I'm just trying to keep it alive. Not everyone on here realises that this may help a lot of sufferers as it is not a tinnitus specific drug.

@Gb3, my last post was March 19th prior to yesterday's. That is 10 days.

If you look I've been trying to update a lot of the dead threads, like Sound Pharmaceuticals, Prof. Thanos Tzounopoulos, etc.

Trying to do my bit on here.

 

I read your posts. Always positive. Thank you for the hope you give us.

 

Just an infograph on side effects from Phase 2 X-Tole study. Look, if it doesn't work for tinnitus, it may work for depression associated with tinnitus. The Mt. Sinai trial results are imminent as is a company sponsored Phase 2. This is good news as we all know SSRIs do cause or exacerbate tinnitus. I consider the side effect data here to be relatively low vs. that of placebo. Certainly lower than that of Retigabine and lower than most SSRIs.



There is great hope in this drug for tinnitus sufferers based on the Retigabine information and Prof. Thanos's work on reformulating the same compound. Still no response or comment on XEN1101 from Prof. Thanos or his team. I emailed five of them for comment. If anyone has the possibility of getting a comment from Prof. Thanos on the potential for XEN1101 to treat tinnitus, please do so. It would be amazing to get the opinion of an expert on Retigabine. It was such a missed opportunity in the Tinnitus Talk Podcast interview unfortunately.

 

Thanks Deb. I am considered a pariah on the Frequency Therapeutics threads for my balanced view but I firmly believe there is so much hope for a tinnitus specific treatment in the next 2-3 years. It is what keeps me going on a daily basis! Hope you are well.

 

Once they announce an actual trial for tinnitus, this thread will explode.

 

It would be great if some depressed tinnitus patients got on the Phase 2 depression trial in the meantime, but I think a trial for tinnitus specifically is some way off.

 

If there is a trial location nearby, I will try to participate. I have been prescribed antidepressants and benzos to sleep so I would be the perfect candidate.

 

Same as me. Trying to cut the SSRIs. Slowest taper from 40 mg Paxil ever but down to 6 mg now. Mirtazapine for sleep works amazing at 7.5 mg. Still need Diazepam to get me through the day though.

The Phase 2 at Mt. Sinai is still recruiting for depression.

XEN1101 for Major Depressive Disorder

Nothing on the depression company sponsored trial for a few months I think.

For anyone in New York here are the contact details:

Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029

Contact:
Sara Hameed, B.A.
212-585-4622
sara.hameed@mssm.edu

Contact:
Amelia Karim
212-585-4621
amelia.karim@mssm.edu​

For anyone in Texas here are the contact details:

Baylor College of Medicine
Houston, Texas, United States, 77030

Contact:
Tabish Iqbal
713-798-4095
tiqbal@bcm.edu​

I would be great to get someone from the forum on the trial.

 

@Padraigh Griffin, why do you cut your SSRI before the benzo?

I am also on SSRI and a benzo called Oxazepam (30 mg a day). I want to cut the benzo out before the SSRI.

I also use Zopiclone for sleep.

Just curious about your thoughts?

 

Hey. I'm no expert but it has been scientifically proven that SSRIs cause tinnitus. A poster recently put up six studies confirming that fact. Here is one article. This is out of a University in Oregon and they have multiple studies on this.

Study Suggests Serotonin May Worsen Tinnitus

Zopiclone should not be used for sleep for long periods from my research, but hey, if it works, then keep on it bro.

In my case, lucky me, I was put on Paxil at very high doses when I had my sleep induced psychosis (sound's scary that word psychosis, but thankfully mine was a once off from lack of sleep) but I just developed total insomnia in a period of intense stress (think two babies and a father on ventilators). I tried to be a superhero and keep a vigil but ended up with a complete physical breakdown. I was working full time as well trying to pay the bills. Was just mad.

Anyway, buddy, to keep a long story short, here is a snippet from an article from the ATA written by Neil Bauman, PhD, who has written well over 160 articles on ototoxicity and is considered the world's leading expert on the subject.



You can see lucky me and my lovely Paxil (Paroxetine) sitting there in number 3. Apparently it is the SSRI with the most potent affinity for serotonin receptors and yes we have some of these lovely serotonin receptors in our Dorsal Cochlear Nucleus. That is where a lot of tinnitus researchers believe tinnitus emerges from. It is the last point of entry for sound into the brain.

Also, severe disruption in serotonin can also mess up your Potassium channels which aligns with the DCN theory.

It is a tough call regarding benzos. I know they are shit but I need them as my tinnitus is messed up. I was on Clonazepam at 1 mg and managed to taper from 1 mg (20 mg Diazepam equivalent) to 20 mg of Diazepam, and down to 8 mg of Diazepam, however I've nudged up to 12 mg again. I tapered from 20 mg to 8 mg during a period where I had two middle ear surgeries and I reckon I can taper again no problem (fingers crossed), but I am dying to kick the tinnitus provoking Paroxetine but taking it slow as withdrawal from it can be very very severe (worse than benzos even). I'm on 7 mg and tip toeing down and will jump at 1 mg towards end of summer (if I can).

Anyway, sorry for the essay. Hope it helps

 

@Padraigh Griffin, please keep posting the updates. Thank you!

I too think that there will be a drug that helps tinnitus, but it's going to be an off-label use of a drug designed to do something else.