Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

What is the main focus of the Phase 3 trial? Safety or efficacy? Trobalt had some really nasty side effects which ended up getting it pulled from the market so maybe a Phase 3 is a good thing.

 

Phase 1 is where safety is predominately tested. Thus this would mean that the treatment would have likely either got canned or been made to fix the safety issues first before it could proceed further if it was deemed to be unsafe at this point.

Phase 2 and 3 are primarily efficacy trials. While these stages do look at any safety issues which may arise and also may act on them if they are significant, they are not the primary purpose of the trial and are also not heavily scrutinised too.

 

Didn't Trobalt pass a safety test, only to reveal major side affects later on?

 

Does anyone know what is the difference between XEN-1101 and OTO-313? Don't they target the same potassium channel?

 

Somebody more knowledgeable may chime in, but my understanding is that OTO-313 is injected intratympanically post acoustic trauma in order to reduce hyper-activity in some way. While XEN-1101 on the other hand is not meant to be injected into the ear but may reduce the hyper-activity in the brain/auditory cortex/associated pathways. Since tinnitus seems to be a brain problem, while having a peripheral cause, I believe XEN-1101 may help chronic sufferers more effectively than OTO-313, but it's all my speculation and I don't know anything for sure.

Stacken

 

I believe it might have hence how I stated that there tends to be an analysis of safety outcomes if it is required.

 

I don't know what you guys are getting so worked up for, they are targeting epilepsy, not tinnitus. Even if the drug works, it should only work for epilepsy, or not?

Also how are you planning to get the drug? Are you going to tell a doctor you have epilepsy?

 

Because it is based off another drug that was apparently quite effective for tinnitus but unfortunately had too many side effects and had to be pulled. The idea is that they have tweaked it enough to ditch the side effects but remain effective against tinnitus. I think...

 

Do a bit of poking on this site for Trobalt. It evidently really worked for some people. It was pulled because of dangerous side effects. Doctors can and do approve drugs for off-label use all the time. With any luck this works as well or better than Trobalt and it doesn't turn you blue.

 

So is the drug Thanos Tzounopoulos is working on the same thing?

 

I’m not the expert but it sure sounds like they are working on something very similar. I think with him it is particularly for tinnitus.

 

Yes, the drug Thanos is working on is a reformulation of Trobalt, with a lot more specific function and potency. He is a long way off market yet and hasn’t started clinical trials. Tinnitus Talk Podcast has a very good interview with him. Worth a listen.

 

Yes but how do you know that those side effects were not part of the working formula? Maybe if you remove some of the formula it doesn´t work for tinnitus anymore. Also for how many has it worked? Danny Boy reported that his tinnitus came back after a while.

So it´s not a solution for a longer period; only a short break.

And those drugs usually have bad side effects when taken if you don´t have epilepsy, worst case is something worse is going to happen to you.

It´s still a lottery.

 

Of course we don't know whether this will work for tinnitus or not, if it will be more or less effective, or if it will ultimately be approved. I mean right now nothing in this world works which is why I follow these things hoping one of them works out by hook or crook. All we do know is that the previous unsafe version of this apparently did something for some people, so time will tell if this has any use to us at all.

That being said I did have a poke about their website and they are suggesting there were other potential uses for this than just epilepsy. I'd have to go back and take look at what they were hoping this could potentially be used for. I know that tinnitus wasn't mentioned.

 

Oh then there was FX-322. Hey! Wait a minute...

 

I find your knowledge impressive but I'm kind of cautious by nature. I wait till I see the body-count or the number of people who are cured or the number who show improvement. As a matter of fact just a tiny-little improvement for me to lead a relatively normal life would have me more than satisfied and it would ease the time of the years going by till they get a 100% cure.

Ah yes, the 'fada': As an accomplished scholar I can state that (with a regular Microsoft keyboard) you gotta press "Alt Gr" on the lower right hand side + the "a" or other vowel you want. Doing this for a capital letter gets trickier: You have to press at the same time the Shift, the Alt Gr and the vowel of your choice.

I hope this helps.

 

The Phase 3 trial for XEN1101 is planned for H2 next year.

Xenon Pharmaceuticals Reports Third Quarter 2021 Financial Results and Provides Corporate Update

 

How many phases before FDA approval and commercialisation?

 

As far as I know, Phase 3 is the last one. There is something called "Phase 4", but that's a follow-up of the drug once released.

 

According to this article...

Xenon’s XEN1101 for focal epilepsy has likely positive Phase II, but doubt on ability to produce seizure freedom and long-term success potential

...this drug is tested for epilepsy, not tinnitus. The article says that the effectiveness for epilepsy is moderate (seizures are not prevented).

I hope it will work for tinnitus but the current trials are not testing this it seems.

 

Probably 24-30 months away from commercialisation if it does a good Phase 3. That’s probably being optimistic.

Being investigated for depression too. Will be very interesting from a cost perspective if it does well in that area. SSRI alternative. Badly needed as SSRIs are shit drugs and decades old.

 

Do we know which KV channels Xenon are targeting?

 

We do, certainly more selective than Trobalt. I forget which ones, but if you go through the thread or their presentations, you will find the info.

 

Think it's Kv7.

 

KNCQ1 Kv 7.1 7.2.

Their current formulation in Phase 3 is basically Trobalt with a single different group attached. I wouldn't hold out hope that one will be serious side effect free but should work likewise as Trobalt did for people.

Another version will be out which should be better. I think its structure is totally different.

 

Sorry. Is Phase 3 the final trial before commercialisation?

 

Also its formulation is far more potent than Trobalt. A lot less drug for far more efficacy. This is a critical point. It is not only more selective but is a way more potent at lower doses. Hopefully this will significantly reduce the side effect burden.

 

Yes. It should be.

 

How long will Phase 3 take though?

 

Honestly, I don’t know. I’d say 2024 before this drug hits the market at the earliest. I researched it comprehensively prior to my MEM diagnosis. The presentations on their website are excellent. 20 mg is the dose they are targeting but off label for tinnitus, who knows? The only evidence we have is that Trobalt worked for some plus it ties in with Dr. Susan Shore’s hyperexcitability theory.