Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

The idea would be to hold out here with XEN-1101 as a palliative treatment until regenerative drugs come on to the market.

 

Haha, I would also have to lie to take part in the study because my depression is severely severe, so I would have to lie that I only have moderate depression. I would not falsify the results. Haha, my psychotherapist (actually quite a good one) also says I should downplay the stressful things (can't do with 9/10 tinnitus, 24/7) lol.

 

I wouldn’t have to lie. I have symptoms of MDD and PTSD. My biggest concern about the upcoming clinical trial(s) for this is that it looks like MRIs might be a requirement, as they want to image the brain as part of the study. With severe tinnitus and hyperacusis, MRIs would be a no-no.

 

If I had tinnitus alone I would never even consider lying to participate in a trial.

I've had tinnitus for a long time, and even though I've been through some excruciatingly dark moments, I've managed to function with it at least somewhat.

What I cannot do is reconciling chronic hyperacusis with a somewhat normal life. It's just not possible.

 

Found this study:

The Role of Inflammation in Tinnitus: A Systematic Review and Meta-Analysis

Maybe someone has some insight on it! Potassium channel modulators are not mentioned, but they do say this:

''Accumulating evidence suggests that inflammation plays a role in the pathogenesis of subjective tinnitus. Noise exposure and salicylate administration both lead to inflammation throughout the whole auditory pathway. In particular, TNF-α, IL-1β, glia and activated platelets are associated with acute tinnitus. TNF-α and IL-1β influence NMDA and GABAA receptors, leading to an increased excitatory and decreased inhibitory neurotransmission. These changes can lead to neuroplasticity and thus chronic tinnitus. Whether inflammatory mediators still play a role in chronic tinnitus remains to be elucidated. Nevertheless, drugs targeting the involved inflammatory mediators could be a potential effective treatment for (acute) tinnitus.''​

So how can potassium channel modulators help if there are so many other inflammatory factors that can alter neuroplasticity and therefore sustain chronic tinnitus?

 

They have quiet MRIs. Look for Siemens Quiet Suite.

 

Phase 2 trial for depression starting now/soon. Results will be provided sometime next year.

Xenon Pharmaceuticals Announces Initiation of Phase 2 Clinical Trial to Evaluate XEN1101 as a Treatment for Major Depressive Disorder (MDD)

 

Very promising press release regarding the depression study.

 

What I like is the fact that Xenon does not BS around with publishing papers, peer reviewing before publishing results etc. Commercial companies with an incentive for business is what will drive the treatments. They won't hesitate with their FDA submissions once the trials are over.

I'm also excited about Oxytocin. It provided 25% reduction against placebo in a small study, it is widely available and does not require FDA approvals. The study closes 6th of May and I don't expect them to take years to come with the results. Might be our first temporary relief. Not sure why it gets so little attention. This treatment is the furthest in the entire tinnitus pipeline.

 

So if the stars are all aligned with respect to outcomes for this and future trials, is 2024 a reasonable guess as to when it might appear on the market?

 

So can we get Oxytocin from the market as of now?

 

They are using high dosage, not sure what the other ingredients are but it is a well documented substance which is used during giving birth etc. I would wait a few months until the study results are published.

 

Xenon Pharmaceuticals is Canadian. I wonder if it will be released first in the United States before Canada or at the same time. They did trial the drug here and there.

 

This is my guess. I feel there is a 90% chance of it being released as an epilepsy drug in mid 2024. Then I think it will follow quickly for depression as they will have accumulated enough efficacy and safety data from the various trials to market it for depression.

When already on the market for epilepsy, will a Phase 3 trial for depression even be necessary?

Maybe someone with better knowledge than I can clarify this.

 

Could you get it without a prescription so I could buy it for tinnitus? What do you think about the price? When a company is private I know they are free to go on market with a price that will allow them to recover their costs, so the price can be high?

That of course will go against my first sentence, so probably the drug will not be covered by insurance!

Another question that is in my mind, does this drug modulate the potassium channels of all the cranial nerves or is it so selective that it modulates the auditory nerve only?

 

I've read an analysis somewhere that it has the potential to be priced around €80,000 EUR per year. Cannot find the exact wording but there is a very interesting analysis on XEN1101 / XEN496 here:

Xenon Pharmaceuticals, Inc. (XENE) - INITIATION REPORT (PDF)

 

And for what potassium channels they work on? For which nerves...? Some of us have sensory tinnitus...

 

I am totally clueless on the pharmaceutical industry and healthcare in America, but my god that price is depressing. Would people actually have to buy that out of their own pocket? In that case I'd rather go full Walter White mode and cook something up myself. Or shoot some Quercetin up my bum...

 

XEN496 might be priced high as it is a niche market, with a severe need for treatment.

XEN1101 has many competitors for focal epilepsy treatment and if it's going after the depression market it will not be priced relatively high in my opinion.

 

Very detailed paper on the positive effects of Ezogabaine for the treatment of MDD:

https://cdasr.mclean.harvard.edu/wp-content/uploads/2021/05/Costi_AJP21-2.pdf

It was referenced in the Xenon PR.

Here is the bottom line for anyone who does not want to read the full document:





Based on a 900-mg dosage of Ezogabine.

 

A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder (X-NOVA)

XEN1101 Phase 2 for depression started as of yesterday, lasting one year. Location is in California US.

 

Great, so we are on the road for depression. Let us see what that brings. I wonder will they publish the Mt. Sinai trial results?

 

Need more updates!

 

Since they did Canadian trials too, Health Canada will have this approved quicker than the FDA I bet...

 

Wonder if we can apply for compassionate use, but given they aren't testing "tinnitus/hearing damage" I'm kind of doubting it, unless we had a comorbidity related to one of their seizure studies.

Their Phase 2 was a bombshell of good news for focal seizures, so that leads me forward with hope as opposed to so many of these borderline significant other drugs.

 

I tried to read more about on Trobalt. I only saw people get half an hour of relief unless I'm not reading it right.

And I do see eye issues still mentioned in the new data released on Xenon, so I continue to be worried about visual snow.

 

I see that XEN496 is not a copy paste of Trobalt but they are also addressing pigmentation issues. I always thought this was generically the same.

Old news post:
Xenon Expands Ion Channel Neurology Pipeline with Addition of XEN496, a “Phase 3 Ready” Potassium Channel Modulator for the Treatment of Epilepsy

Xenon is working on a pediatric-specific formulation for XEN496 that may also address certain pigmentation issues associated with ezogabine.​

Is anyone going to give this a go once on the market or do you patiently wait another year? I see no report on any EMA designation, only FDA.

 

Will they be eligible for compassionate use?

 

The trial ends in a couple of months. Xenon is very fast in their reporting and publication of results. Since this is an existing compound not sure if it has to go through a new FDA approval. There are no expanded access programs but I doubt compassionate use will go much faster then waiting for the Phase 3 to complete. There are no trials needed after this one.

 

I think you read it right; IIRC it lasted longer for some people, but nevertheless you are right that it doesn't last indefinitely. The hope is that the new drugs would last longer since they're more potent. In his Tinnitus Talk Podcast appearance, Thanos Tzounopoulos also suggested that these drugs could give the brain a chance to recalibrate and recover, which could further increase tinnitus suppression.

I'm really curious to see what are the (hopefully beneficial) effects of taking Kv channels drugs in the long term. I can easily see a scenario where these drugs suppress tinnitus for many hours, so they'd become something you take everyday. Personally, I wouldn't have a problem with that.

I though neither of their drugs were Trobalt copypastes; that they both were more selective and more potent, but I don't really understand the difference between XEN1101 and XEN496.