Reformulated Retigabine (Trobalt): BHV-7000, a Kv7.2 Modulator by Biohaven (Pfizer)

Discussion in 'Research News' started by InNeedOfHelp, Nov 14, 2022.

    1. Nick47

      Nick47 Member Benefactor

      Location:
      UK
      Tinnitus Since:
      2015
      Cause of Tinnitus:
      Viral/noise
      @StoneInFocus, is this still your view?
       
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    2. StoneInFocus
      Badass

      StoneInFocus Member

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Hearing damage, ear infections
      No, because I haven't investigated Susan Shore's device enough to say anything sensible about it. I'm a bit out of the loop right now. Anything happen?
       
    3. Nick47

      Nick47 Member Benefactor

      Location:
      UK
      Tinnitus Since:
      2015
      Cause of Tinnitus:
      Viral/noise
    4. AUTHOR
      AUTHOR
      InNeedOfHelp

      InNeedOfHelp Member

      Tinnitus Since:
      08/2021
      Cause of Tinnitus:
      MRI Scan
      Biohaven updated their pipeline for BHV-7000 Kv7.2. They are going to run four trials at once.

      - Focal Epilepsy, Phase 1
      - KCNQ2-DEE, Phase 1
      - Mood Disorders, Phase 1
      - Pain Disorders, Phase 1

      I don't see the trials yet on ClinicalTrials.gov.

      I'm not based in the US so I cannot apply, unfortunately.
       
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    5. CRGC
      No Mood

      CRGC Member

      Location:
      Montreal
      Tinnitus Since:
      06/2022
      Cause of Tinnitus:
      SNRI/Noise
      Thanks for the information! I wonder if hyperacusis / noxacusis sufferers would qualify for the chronic pain study.
       
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    6. DimLeb

      DimLeb Member

      Tinnitus Since:
      03/2021
      Cause of Tinnitus:
      Idiopathic Cochleopathy or Maybe Loud Music
      So no hope for tinnitus?
       
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    7. ploughna

      ploughna Member

      Tinnitus Since:
      2017
      Cause of Tinnitus:
      motor racing and power tools
      I definitely would not say that - their latest presentation states:

      "Broad Potential in Adjacent Indications: Warrants further evaluation in BPD, depression, pain, others".​

      So might qualify under 'mood disorders' for the upcoming trials, or one of these other indications such as depression later (and with a bit of luck, maybe tinnitus will appear in the 'others' category). They also have a compassionate use program, so I'd say there are a number of paths to gain access.

      Also, interesting to see they claim to have a differentiated formulation to the competition (meaning XEN1101):

      "Pursuing Differentiation: Dialing out GABArisk (somnolence, sedation, dizziness) without impacting efficacy"​

      See here: https://ir.biohaven.com/static-files/2dfd9a38-a99c-460e-a27b-6b6ca537f4e1

      It goes into a lot more detail on the advantages over XEN1101.
       
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    8. KoolKat

      KoolKat Member

      Location:
      USA
      Tinnitus Since:
      2013
      Cause of Tinnitus:
      HeadPhones/ Noise induced
      So basically we are hitching a ride and hoping for a glitch in the matrix.
       
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    9. CRGC
      No Mood

      CRGC Member

      Location:
      Montreal
      Tinnitus Since:
      06/2022
      Cause of Tinnitus:
      SNRI/Noise
      I'm inclined to believe the chances of Kv7 modulators helping with tinnitus are bigger than "a glitch in the matrix", but you're right about us once again having to hitch a ride on something designed primarily for another condition. This seems to be a recurring theme with potential pharmaceutical cures. Until the mechanics behind tinnitus are better understood, it looks like too big of a risk for a pharmaceutical company to pursue treatments specifically for our issues: Otonomy's failure and dissolution is the latest example of that.
       
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    10. CRGC
      No Mood

      CRGC Member

      Location:
      Montreal
      Tinnitus Since:
      06/2022
      Cause of Tinnitus:
      SNRI/Noise
      That's a very interesting detail you highlighted here. There's a significant difference between this drug and XEN1101/Trobalt, and that is that the latter also affect GABA receptors. As many users' testimonials have highlighted, GABA-affecting substances (benzos, alcohol...) seem to help with certain forms of tinnitus. Could it be that Trobalt's benefit for tinnitus sufferers lied not in its Kv7 modulating properties but rather in its effect on GABA? If that was the case, then that could mean that XEN1101 would be the winner for us.
       
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    11. ploughna

      ploughna Member

      Tinnitus Since:
      2017
      Cause of Tinnitus:
      motor racing and power tools
      The research seems to point to KCNQ2/3 potassium channels as the primary mechanism. I haven't personally seen much on the GABA aspect but you have a good point. If both drugs make it to market, we may have an opportunity to find out!

      Dr. Tzounopoulos' work has verified the action of KCNQ2/3 channels in animal models with RL-81 which is also a highly selective potassium channel activator (no mention of GABA):

      RL-81 Could Be Promising Drug Candidate for Noise-Induced Tinnitus

      What I like about BHV-7000 is that it's much more potent and more selective than the others, meaning a much smaller dose for equivalent effect, which means much less potential for undesirable side effects.

      And I also like that the Biohaven team have an impressive track record of success, getting product to market quickly with multiple parallel trials, etc. They see themselves in a race to market with Xenon Pharmaceuticals.

      EDIT:

      On the GABA point above, worth to mention that there are a number of GABA agonist drugs already available that could be taken in combination with BHV-7000 if that turned out to be of any benefit. My money is on the KCNQ2/3 channels being the dominant factor, but the good news is that we'll probably get to find out in the next 1-2 years.

      It'd be great if Prof. Tzounopoulos would come back on Tinnitus Talk Podcast for a follow-up interview. How similar is it and is he even still pursuing RL-81 anymore given Xenon Pharmaceuticals and Biohaven are planning a very similar drug? @Padraigh Griffin (RIP) was unsuccessful in getting an answer to this question despite multiple attempts.
       
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    12. ploughna

      ploughna Member

      Tinnitus Since:
      2017
      Cause of Tinnitus:
      motor racing and power tools
      From their latest investor deck in January - moving quickly:

      upload_2023-1-30_20-40-34.png
       
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    13. Stayinghopeful
      Procrastinating

      Stayinghopeful Member

      Location:
      NSW, Australia
      Tinnitus Since:
      06/2022
      Cause of Tinnitus:
      COVID-19 / Anesthesia
      Great news. I hope it happens early in H2!
       
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    14. Nick47

      Nick47 Member Benefactor

      Location:
      UK
      Tinnitus Since:
      2015
      Cause of Tinnitus:
      Viral/noise
      There are five different kinds of KCNQ potassium channels in the body, but only two are important in epilepsy and tinnitus: KCNQ2 and KCNQ3. The problem with Retigabine is that it acts on other KCNQ potassium channels as well. That's why it has so many unwanted side effects.

      In terms of the aggressive schedule, well that's what happens when a big pharmaceutical company gets involved in our space. It may be good news for some of us as it has pushed other smaller companies like Xenon Pharmaceuticals to crack on due to competition.
       
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