1st Order Pharmaceuticals Inc: 1OP-2198

[Mic]

I've gotten in touch with someone that has tinnitus who said they will be in the XEN1101 phase 1 trial. Looking forward to their experience.

Don't get disappointed if phase 1 doesn't show a noticeable effect for tinnitus. Phase 1 trails are purely intended as a safety check for drug candidates. The dosing could therefore be lower than the therapeutic value needed for effective treatment.

Phase 2 will be important because it's goal to prove effectiveness on tolerable dosing of the drug for humans.

 

[vermillion]

I am a little bit confused. Does this medication affects KCNQ2/3 or only KCNQ2?

Don't get disappointed if phase 1 doesn't show a noticeable effect for tinnitus. Phase 1 trails are purely intended as a safety check for drug candidates. The dosing could therefore be lower than the therapeutic value needed for effective treatment.

On top of that we don't know his tinnitus pathogenesis/sub-type.

 

[Danny Boy]

I am a little bit confused. Does this medication affects KCNQ2/3 or only KCNQ2?

On top of that we don't know his tinnitus pathogenesis/sub-type.

I have no clue, as I couldn't find any information which channels they are going to use. But their original video mentions KV7.2 and 3. Website lists tinnitus, so I would expect this is the channels they are targeting.

 

[acufenero]

Tinnitus is now officially mentioned as potential indication for XEN1101, though they haven't disclosed any concrete plan for a specific trial yet. As we already knew, phase 1 is expected to be completed in the first half of 2018, with phase 2 starting right after.

Xenon Pharmaceuticals Outlines Key Milestones for 2018

• XEN1101 is a Kv7 potassium channel opener being developed for the treatment of epilepsy and potentially other neurologic disorders. Pre-clinically, XEN1101 has demonstrated improved pharmacokinetics, selectivity, potency and efficacy over ezogabine, an earlier generation potassium channel modulator. Xenon has initiated a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability and pharmacokinetics of both single ascending doses and multiple ascending doses of XEN1101 in healthy subjects. The XEN1101 Phase 1 clinical trial includes a pharmacodynamic read-out incorporating a TMS model, which is designed to demonstrate activity of XEN1101 in the central nervous system by observing a change in an EEG (otherwise known as an electroencephalogram) or an EMG (otherwise known as an electromyogram) signal. By mid-year, we expect to have Phase 1 clinical results. A Phase 2 proof-of-concept trial evaluating XEN1101's efficacy as a treatment for adult focal seizures is anticipated to begin in the second half of 2018, with a parallel plan to advance XEN1101 as soon as feasible thereafter into rare, pediatric forms of epilepsy, such as EIEE7, an early infantile epileptic encephalopathy associated with mutations in the KCNQ2 gene causing a loss-of-function in the Kv7.2 potassium channel. XEN1101 potentially addresses the primary cause of this severe encephalopathy by augmenting the defective Kv7.2 channel. Other potential indications for XEN1101 include tinnitus and ALS.

 

[Paulmanlike]

Tinnitus is now officially mentioned as potential indication for XEN1101, though they haven't disclosed any concrete plan for a specific trial yet. As we already knew, phase 1 is expected to be completed in the first half of 2018, with phase 2 starting right after.

Xenon Pharmaceuticals Outlines Key Milestones for 2018

• XEN1101 is a Kv7 potassium channel opener being developed for the treatment of epilepsy and potentially other neurologic disorders. Pre-clinically, XEN1101 has demonstrated improved pharmacokinetics, selectivity, potency and efficacy over ezogabine, an earlier generation potassium channel modulator. Xenon has initiated a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability and pharmacokinetics of both single ascending doses and multiple ascending doses of XEN1101 in healthy subjects. The XEN1101 Phase 1 clinical trial includes a pharmacodynamic read-out incorporating a TMS model, which is designed to demonstrate activity of XEN1101 in the central nervous system by observing a change in an EEG (otherwise known as an electroencephalogram) or an EMG (otherwise known as an electromyogram) signal. By mid-year, we expect to have Phase 1 clinical results. A Phase 2 proof-of-concept trial evaluating XEN1101's efficacy as a treatment for adult focal seizures is anticipated to begin in the second half of 2018, with a parallel plan to advance XEN1101 as soon as feasible thereafter into rare, pediatric forms of epilepsy, such as EIEE7, an early infantile epileptic encephalopathy associated with mutations in the KCNQ2 gene causing a loss-of-function in the Kv7.2 potassium channel. XEN1101 potentially addresses the primary cause of this severe encephalopathy by augmenting the defective Kv7.2 channel. Other potential indications for XEN1101 include tinnitus and ALS.

This isn't new news, it was mentioned as a 'potential' indication ages ago.

 

[vermillion]

This isn't new news, it was mentioned as a 'potential' indication ages ago.

they didn't have it on their website.

 

[Mic]

Just a quick update regarding XEN1101. Recruitment for the phase 1 trail has apparently started a month ago @RichardsonLab in London:

http://epilepsy-london.org/clinical-trial-new-anti-epileptic-drug/

 

[Autumnly]

Press Release, Xenon, March 7th 2018
http://investor.xenon-pharma.com/phoenix.zhtml?c=253202&p=irol-newsArticle&ID=2336851

• Xenon has completed a Phase 1a pilot TMS study in 8 healthy subjects and has now begun a double-blind, placebo-controlled, randomized cross-over Phase 1b TMS study in 15 healthy subjects.
• Xenon expects to present interim Phase 1 results – including preliminary pharmacokinetic, tolerability and safety data from 42 subjects, along with a read-out from the Phase 1a pilot TMS study – at the 14th EILAT Conference on New Antiepileptic Drugs and Devices to be held in Madrid, Spain in May 2018.
• The release of the complete Phase 1 results, including the Phase 1b TMS data, is anticipated in the second half of 2018.
• Xenon anticipates initiating a Phase 2 proof-of-concept trial evaluating XEN1101's efficacy as a treatment for adult focal seizures by year end.
• Xenon also intends to explore a parallel plan to advance XEN1101 into rare, pediatric forms of epilepsy as soon as feasible thereafter.

 

[NatureHiker]

Hi, I just got word from the guy I messaged who is in the Xen1101 phase 1. They're running a double blind, so you don't know what you're taking, but apparently one of the drugs he took led to an 80% reduction in his tinnitus. No serious reactions after taking the drug neither.

 

[Stakovic]

Hi, I just got word from the guy I messaged who is in the Xen1101 phase 1. They're running a double blind, so you don't know what you're taking, but apparently one of the drugs he took led to an 80% reduction in his tinnitus. No serious reactions after taking the drug neither.

Invite this guy to join Tinnitus Talk?

 

[Pleasure_Paulie]

Hi, I just got word from the guy I messaged who is in the Xen1101 phase 1. They're running a double blind, so you don't know what you're taking, but apparently one of the drugs he took led to an 80% reduction in his tinnitus. No serious reactions after taking the drug neither.

That's really fascinating as its only speculation if this drug has the same effect on tinnitus that Trobalt did.

 

[Mic]

but apparently one of the drugs he took led to an 80% reduction in his tinnitus.

Good news, but dont forget:

• One case is no case.
• Placebo is often a good but temporary remedy.
• The internet is full of trolls.

 

[jer]

@NatureHiker it's probably best not to publicly disclose any facts/rumors about the trial you have learned somewhere. This could potentially affect the outcome of the trial, and I am sure we all want this to succeed.

 

[NatureHiker]

@NatureHiker it's probably best not to publicly disclose any facts/rumors about the trial you have learned somewhere. This could potentially affect the outcome of the trial, and I am sure we all want this to succeed.

Noted. I agree it's best to let the researchers release the news about the trials when they're ready.

 

[Danny Boy]

Noted. I agree it's best to let the researchers release the news about the trials when they're ready.

This isn't a trial for tinnitus though?

 

[Mic]

This is the official clinicaltrails.gov page for the phase 1 trail of XEN1101 (with TMS):

https://clinicaltrials.gov/ct2/show/NCT03468725

The fact that they included TMS to check for empirical evidence of drug delivery in the brain is a real game changer and gives confidence in the professionality of the research team.

No nonsense about subjectively measuring (placebo) effects at people using the drug but gathering factual evidence to make real causal connections (and not vague correlations) between the drug and it's promised effect.

Chapeau Xenon... chapeau...

 

[Autumnly]

Xenon Provides Corporate Update and Overview of XEN1101 and XEN901 Presentations at 14th Eilat Conference

• XEN1101 Presentation from 14th Eilat Conference on May 15, 2018

• Xenon Presents Positive XEN1101 TMS Pharmacodynamic Phase 1 Data at 14th Eilat Conference

 

[Stakovic]

Hi, I just got word from the guy I messaged who is in the Xen1101 phase 1. They're running a double blind, so you don't know what you're taking, but apparently one of the drugs he took led to an 80% reduction in his tinnitus. No serious reactions after taking the drug neither.

Are you in touch with the guy who participated in trial?

 

[NatureHiker]

Are you in touch with the guy who participated in trial?

I am and am watching how XEN1101 develops. It looks very promising.

 

[Benoves]

I am and am watching how XEN1101 develops. It looks very promising.

Sounds good. Did his tinnitus reduce a second time because of the drugs? I think this drugs is very promising.

 

[Tigo]

xen1101 is moving to phase II

http://investor.xenon-pharma.com/phoenix.zhtml?c=253202&p=irol-newsArticle&ID=2362563

 

[JohnAdams]

This drug seems scary to me, like it would have side affects.

 

[Autumnly]

Xenon Announces Positive XEN1101 Pharmacodynamic Data from Phase 1b TMS Study (Aug. 29, 2018)

• XEN1101 Demonstrates Statistically Significant Reduction in Corticospinal and Cortical Excitability as Measured by TMS-EMG and TMS-EEG
• XEN1101 Demonstrates Greater Effect on TMS-EMG Resting Motor Threshold at Significantly Lower Dose When Compared to Historical Ezogabine Data
• XEN1101 Phase 2 Clinical Trial in Adult Focal Seizures Expected to be Initiated in Fourth Quarter of 2018

 

[JohnAdams]

Xenon Announces Positive XEN1101 Pharmacodynamic Data from Phase 1b TMS Study (Aug. 29, 2018)

• 
  
  
  • XEN1101 Demonstrates Statistically Significant Reduction in Corticospinal and Cortical Excitability as Measured by TMS-EMG and TMS-EEG
  • XEN1101 Demonstrates Greater Effect on TMS-EMG Resting Motor Threshold at Significantly Lower Dose When Compared to Historical Ezogabine Data
  • XEN1101 Phase 2 Clinical Trial in Adult Focal Seizures Expected to be Initiated in Fourth Quarter of 2018

So tinnitus go away?

 

[Benoves]

Xenon Announces Positive XEN1101 Pharmacodynamic Data from Phase 1b TMS Study (Aug. 29, 2018)

• 
  
  
  • XEN1101 Demonstrates Statistically Significant Reduction in Corticospinal and Cortical Excitability as Measured by TMS-EMG and TMS-EEG
  • XEN1101 Demonstrates Greater Effect on TMS-EMG Resting Motor Threshold at Significantly Lower Dose When Compared to Historical Ezogabine Data
  • XEN1101 Phase 2 Clinical Trial in Adult Focal Seizures Expected to be Initiated in Fourth Quarter of 2018

This drug is very interesting to me. Does @NatureHiker have any updates? Can also Pm me. I really think this is the first relief for some tinnitus sufferers.

 

[Autumnly]

So tinnitus go away?

This medication is for epilepsy, but it could also help with tinnitus as it's a potassium channel opener.
"We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity," Dr. Tzounopoulos said. "These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells." - https://www.sciencedaily.com/releases/2013/05/130527153701.htm

Xen-1101's former version, trobalt (retigabine) was discontinued in June 2017. "In 2013 GSK announced that there were safety issues around the drug as it could cause a blue discolouration of the skin and eye abnormalities. Doctors were urged to review patients prescribed the drug and to re-evaluate benefits versus risk. However now, due to the very limited use of the medicine and the continued decline in new patients being prescribed Trobalt, GSK is discontinuing the medicine on a permanent basis."

 

[Apolonia]

This medication is for epilepsy, but it could also help with tinnitus as it's a potassium channel opener.
"We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity," Dr. Tzounopoulos said. "These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells." - https://www.sciencedaily.com/releases/2013/05/130527153701.htm

Xen-1101's former version, trobalt (retigabine) was discontinued in June 2017. "In 2013 GSK announced that there were safety issues around the drug as it could cause a blue discolouration of the skin and eye abnormalities. Doctors were urged to review patients prescribed the drug and to re-evaluate benefits versus risk. However now, due to the very limited use of the medicine and the continued decline in new patients being prescribed Trobalt, GSK is discontinuing the medicine on a permanent basis."

The guy (Danny Boy) who died recently, did he manage to get rid of tinnitus completely with Trobalt? Or just reduced his tinnitus?

 

[Silvio Sabo]

The guy (Danny Boy) who died recently, did he manage to get rid of tinnitus completely with Trobalt? Or just reduced his tinnitus?

As far as I've read it did reduce his tinnitus but gave him eye problems.

 

[reggie green]

WOW, Danny Boy died wow. What was the cause of his death? I am sorry to hear that, he was a strong advocate of finding a cure.

 

[Autumnly]

Disclaimer: posting this here to ask if anyone knows if this drug could potentially help with tinnitus

Xenon Expands Ion Channel Neurology Pipeline with Addition of XEN496, a "Phase 3 Ready" Potassium Channel Modulator for the Treatment of Epilepsy

• XEN496 (active ingredient ezogabine) is a Kv7 potassium channel modulator for the treatment of epilepsy
• Based on feedback from the FDA, Xenon anticipates initiating a single, pivotal Phase 3 clinical trial enrolling 20 patients in mid-2019 examining XEN496's efficacy
• Ezogabine, also known as retigabine, is the only anti-epileptic drug previously approved by the FDA. GlaxoSmithKline (NYSE:GSK) marketed ezogabine as Potiga in the U.S. and Trobalt in Europe but withdrew the drug from the market worldwide in June 2017 citing commercial reasons.
• The Company have obtained a right of reference authorization from GSK for FDA's reference to support its regulatory submissions and have also received ODD from the FDA for XEN496 as a treatment of KCNQ2-EE.