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

[InNeedOfHelp]

In the last Xenon Pharmaceuticals conference call they named BHV-7000 a direct competitor for XEN1101.

BHV-7000 is a reformulated, more potent version of Trobalt/Retigabine.

Pfizer acquired Biohaven which brings big pharma to this development space.

BHV-7000 is currently in Phase 1 but is expecting to launch a Phase 2 and Phase 3 in parallel next year to launch simultaneously with Xenon Pharmaceuticals' XEN1101. Seems like a first to market competition. Xenon Pharmaceuticals mentioned in their call last week that the Phase 3 will be hopefully shorter than the Phase 2 trial that lasted 2.5 years.

Biohaven actually has a compassionate use program which Xenon Pharmaceuticals does not have.

Biohaven Sets New Course Following Pfizer Acquisition:

Biohaven Pharmaceuticals has set a new course following its acquisition by Pfizer with a focus on developing therapeutics that modulate the Kv7 Ion Channel for the treatment of neurological and neuropsychiatric diseases.

The company officially launched Tuesday as a new spin-off entity with more than 13 clinical and preclinical programs. Biohaven's primary focus will be developing treatments for neurological and rare disorders including epilepsy, pain and mood disorders, obsessive-compulsive disorder, spinocerebellar ataxia and spinal muscular atrophy.

The new Biohaven launches with approximately $257.8 million in cash.

The seeds for this new path were established earlier this year with the acquisition of Channel Bio, a subsidiary of Knopp Biosciences. This brought in the experimental epilepsy treatment BHV-7000, which targets the Kv7 ion pathway. BHV-7000 is currently in Phase I development for multiple indications.

Biohaven Chief Executive Officer Vlad Coric told BioSpace the future looks bright for the new phase of the company. He noted that the drugs targeting the Kv7 ion pathway will be the centerpiece of the company. Coric explained that previously conducted studies showed the efficacy of this approach in treating epileptic seizures

Vlad Coric charts course for new Biohaven with neuroscience push and Big Pharma vets on board:

Deficits in Kv7, a potassium-gated ion channel, result in hyperexcitable neu
rons, which can then lead to seizure in those with epilepsy, Coric explained. Biohaven is looking to normalize those hyperactive neurons, thus reducing seizures with minimal side effects.

Xenon Pharmaceuticals released topline data on its own Kv7 candidate in adult focal epilepsy last year, demonstrating that treatment with XEN1101 led to a significant reduction from baseline in monthly seizure frequency compared to placebo (p<0.001).

"There was data out last year from Xenon demonstrating increased efficacy compared to the older anticonvulsants and a better safety profile, and so we believe the Kv7 mechanism has been de-risked," he said.

Coric isn't worried about the competition, though. He's planning on launching two parallel Phase II/III trials next year, comparing the situation to Ubrelvy, which beat Nurtec to market as an acute migraine treatment.

"It's kind of like when you look back to what we did with Nurtec," he said. "We know Ubrelvy was a little bit ahead of us at Allergan/AbbVie. We ran three parallel trials so if they were positive we could file, and then we ended up launching around the same time."

 

[CRGC]

Very interesting and exciting news, thanks for this!

The press release states that "Biohaven's primary focus will be developing treatments for neurological and rare disorders including epilepsy, pain and mood disorders, obsessive-compulsive disorder, spinocerebellar ataxia and spinal muscular atrophy."

I wonder if tinnitus is on their radar?

 

[Nick47]

I wonder if an email to the CEO highlighting the success of Trobalt on tinnitus would increase the likelihood of them conducting a small trial for tinnitus alongside their other indications.

 

[AnthonyMcDonald]

Good. One thing I was afraid of was Xenon Pharmaceuticals jacking up their prices due to having total market domination. This is the biggest, in my opinion, most scientifically-backed "cure" that we have coming our way.

They definitely know about tinnitus. Pfizer loves profits. We are definitely on their radar.

 

[Hottopic29]

They have a compassionate use program for BHV-7000. They are studying it for pain. I think a lot of people with noxacusis might be able to access it through the compassionate use program.

 

[InNeedOfHelp]

Very interesting and exciting news, thanks for this!

The press release states that "Biohaven's primary focus will be developing treatments for neurological and rare disorders including epilepsy, pain and mood disorders, obsessive-compulsive disorder, spinocerebellar ataxia and spinal muscular atrophy."

I wonder if tinnitus is on their radar?

Before it was transformed into BHV-7000 by Biohaven, it was named KB-3061 from Knopp Biosciences: Knopp's preclinical Kv7 platform is directed to small molecule treatments for neonatal epileptic encephalopathy, other rare epilepsies, tinnitus, and neuropathic pain

They are well aware of the tinnitus potential. They are all awaiting an objective tinnitus test in my opinion before trialing.

 

[Nick47]

This is the biggest, in my opinion, most scientifically-backed "cure" that we have coming our way.

Bigger and more scientifically backed than Dr. Susan Shore and colleagues?

 

[Stayinghopeful]

Bigger and more scientifically backed than Dr. Susan Shore and colleagues?

I read they are starting with 250 million, so I'd wager so.

 

[Ela Stefan]

So BHV-7000 is in pre-clinical stage? When are the human clinical trials expected to start?

 

[Nick47]

I read they are starting with 250 million, so I'd wager so.

I don't mean how much money they have, just that they have shown no interest in tinnitus. No study, no findings and no trials.

Pfizer are even bigger but no use to us currently.

 

[Fightthearmy]

The word "compassionate" & the word "tinnitus" = low mutual information value.

 

[StoneInFocus]

Fantastic news. Let's see how its side effects compare to other potassium channel openers such as cannabidiol, XEN1101 and RL-81.

Bigger and more scientifically backed than Dr. Susan Shore and colleagues?

Kv7.2/7.3 channel openers for the treatment of tinnitus are way, way more scientifically sound than Dr. Shore's Auricle device, which is basically glorified acupuncture from what I read of it (please correct me if I'm wrong). A Kv.7.2/3 channel opener has been proven to help prevent the emergence of tinnitus in mice after noise exposure.

By the way, in the title it says that BHV-7000 is a Kv7.2 opener, but according to the website, "BHV-7000 is a potent activator of Kv7.2 [and] Kv7.3."

 

[Nobody19]

I wonder if an email to the CEO highlighting the success of Trobalt on tinnitus would increase the likelihood of them conducting a small trial for tinnitus alongside their other indications.

It is common knowledge that CEOs take business decisions based on mails by random people.

 

[Pharz]

How is this beneficial for tinnitus sufferers?

(Please excuse my lack of knowledge in this field).

 

[AnthonyMcDonald]

Bigger and more scientifically backed than Dr. Susan Shore and colleagues?

Dr. Susan Shore's research supports the fact of the DCN going haywire in tinnitus generation.

 

[Nick47]

Kv7.2/7.3 channel openers for the treatment of tinnitus are way, way more scientifically sound than Dr. Shore's Auricle device, which is basically glorified acupuncture from what I read of it (please correct me if I'm wrong). A Kv.7.2/3 channel opener has been proven to help prevent the emergence of tinnitus in mice after noise exposure.

By the way, in the title it says that BHV-7000 is a Kv7.2 opener, but according to the website, "BHV-7000 is a potent activator of Kv7.2 [and] Kv7.3."

I think you misunderstood if you think Dr. Shore's device is glorified acupuncture. 20 years of scientific research and successful double-blind, sham-controlled trials doesn't lead to acupuncture. Best thing would be to read the thread. You give some good advice in other threads but I plead you to look into this more.

There is nothing more than a hypothesis (although a very reasoned one based on Retigabine) that this BVH-7000 would be helpful. The animal studies look like they are tested on 'acute' conditions only.

Might it work? Look, who knows. Deep down, given the tinnitus market, I always find it difficult to believe - if they thought it would help with tinnitus symptoms - they wouldn't be in trial for that indication.

It is common knowledge that CEOs take business decisions based on mails by random people.

Yes, I see your point regarding email. I was 'shooting' from the hip.

 

[StoneInFocus]

I think you misunderstood if you think Dr. Shore's device is glorified acupuncture. 20 years of scientific research and successful double-blind, sham-controlled trials doesn't lead to acupuncture. Best thing would be to read the thread. You give some good advice in other threads but I plead you to look into this more.

20 years of research doesn't change the fact that is is just electrical pulses that stimulate nerves (not unlike acupuncture) combined with sounds. Appears to me like an experimental treatment with little theory to back its efficacy up. Haven''t seen a single paper describing why or how that is supposed to work for tinnitus. But again I haven't really looked into it too deeply. You could be right. It's foolish to argue about this anyway. And if it works for tinnitus sufferers I'm glad for them, I would definitely try it out too but I don't think it is available in my area yet.

EDIT:

I want to take this back, I just haven't investigated this subject enough to say anything sensible about it. Dr. Susan Shore's method just sounds an awful lot like that treatment in South Korea, and we all know how that went down. But this thread isn't about that anyway.

 

[CRGC]

I haven't really followed the Kv7 modulator threads so apologies if this has been discussed already, but is there any possibility that these classes of drugs could help with hyperacusis?

 

[Hottopic29]

is there any possibility that these classes of drugs could help with hyperacusis?

Yes since it's also used for pain.

 

[Travis Henry]

Is there a chance they would prescribe BHV-7000 for compassionate use? I'd rather do this than Retigabine.

 

[AnthonyMcDonald]

I haven't really followed the Kv7 modulator threads so apologies if this has been discussed already, but is there any possibility that these classes of drugs could help with hyperacusis?

There have been numerous, although anecdotal reports, of complete suppression of noxacusis/loudness hyperacusis with Retigabine, which doesn't target the exact potassium channels we need and is less potent than both of these medications. I'd say there's a very good chance they will help.

There is nothing more than a hypothesis (although a very reasoned one based on Retigabine) that this BVH-7000 would be helpful. The animal studies look like they are tested on 'acute' conditions only.

@Nick47, most people who were massively helped by Retigabine (@Danny Boy, etc) have had tinnitus for months/years before trying it. Albeit the side effects were disastrous. Based on the results of the XEN1101's side effects after the trials, I can say that the side effects aren't bad at all/minimal.

 

[Ela Stefan]

There have been numerous, although anecdotal reports, of complete suppression of noxacusis/loudness hyperacusis with Retigabine, which doesn't target the exact potassium channels we need and is less potent than both of these medications. I'd say there's a very good chance they will help.

@Nick47, most people who were massively helped by Retigabine (@Danny Boy, etc) have had tinnitus for months/years before trying it. Albeit the side effects were disastrous. Based on the results of the XEN1101's side effects after the trials, I can say that the side effects aren't bad at all/minimal.

If XEN1101 and BHV-7000 are targeting Kv 7.2 and 7.3, how much of use will they be? There was a map of the auditory network posted here by you, which states that Kv3.1 channels are much more important to modulate at the inferior colliculus (IC) level.

 

[Sugar_Boy]

When will the first phase of the clinical trial be published?

 

[Christiaan]

I've asked Biohaven if it is considering a BHV-7000 trial for people with tinnitus. This is the company's answer:

Thanks for your comment. The full clinical development program is under discussion.

 

[AnthonyMcDonald]

If XEN1101 and BHV-7000 are targeting Kv 7.2 and 7.3, how much of use will they be? There was a map of the auditory network posted here by you, which states that Kv3.1 channels are much more important to modulate at the inferior colliculus (IC) level.

The IC is insignificant/superficial in the generation of tinnitus compared to the DCN, at least in the research papers I have reviewed.

 

[Travis Henry]

Is there a chance they would prescribe BHV-7000 for compassionate use? I'd rather do this than Retigabine.

Is this a no? I can't get an answer from them. I need it now.

EDIT:

I spoke to the VP, Investor Relations at Biohaven Pharmaceuticals today. Very nice lady. I told her how much the tinnitus community is interested in BHV-7000. I'm hoping she speaks to the higher ups about trialing it for tinnitus. She said she would. I hope it at least gets out there for compassionate use for epilepsy or something. I told her I'd invest $115k just to try it now.

 

[Nobody19]

I told her I'd invest $115k just to try it now.

Invest that in fundamental research instead, like Hyperacusis Research.

 

[Travis Henry]

Invest that in fundamental research instead, like Hyperacusis Research.

I've already donated to Hyperacusis Research.

I was making up that I had $115k. I'd sell my house to get better though.

Do you think they would already offer compassionate use for BHV-7000 for epilepsy? Or any other condition? Or is it still in the developmental phase? I wish I had asked her that.

 

[StoneInFocus]

I need it now.

If you're that desperate, why not just give cannabidiol isolate a shot?

For less than a hundred bucks you can get very pure powder.

It acts on the same potassium channels and the risks are relatively well known. Just make sure to actually get CBD isolate powder, not any full spectrum oil.

MOD EDIT: Further discussion on cannabidiol isolate should be placed in the thread @StoneInFocus linked above, thanks!

 

[InNeedOfHelp]

There was a publication today about BHV-7000 on Seeking Alpha (an investor platform). They are expecting a pivotal trial (Phase 3 or Phase 2/3) to take place in H2 2023. Seems a very aggressive approach. Maybe we are lucky and their patient recruitment is also very aggressive and fast. Did anyone reach out on the compassionate use program yet? If so, I'd recommend pain with tinnitus as the reason, not tinnitus alone.

When Biohaven acquired its Kv7 platform, the lead asset was BVH-7000, a potassium channel activator that exhibited a preclinical profile suggestive of broad efficacy, high selectivity, and significantly reduced GABA-ergic activity, all suggestive of a marked improvement over current (and past) Kv7-targeting therapies.

Backing up a bit, Kv7 is a family of ion channels comprising five subtypes that are preferentially expressed in tissues and organs. Kv7 protein forms a channel that modulates the flow of charged potassium ions across cell membranes, repolarizing nerve cells and resetting them for potential firing. Biohaven is initially targeting the two Kv7 subtypes (Kv7.2/7.3) found in the cortex and hippocampus. Dysfunction of these channels increases the risk of seizure.

There are two Kv7 therapies that are/were on the market and another in the clinic. Potiga (ezogabine) was approved for the treatment of refractory epilepsy in 2011 but was voluntarily withdrawn in 2017 due to poor tolerability and an adverse event profile that included dizziness and somnolence, largely the result of off-target activity at the GABA brain ion channel. The other Kv7-targeted therapy is flupirtine, which is approved in Europe for acute pain but is riddled by liver toxicity issues. Xenon Pharmaceuticals' XEN1101 is undergoing assessment for the treatment of several seizure indications in clinical trials but appears to possess a narrower therapeutic index than BHV-7000 and is menaced by off-target GABA activity.

Like XEN1101, Biohaven believes BHV-7000 will target a broad range of indications – the first being focal epilepsy, a disease afflicting ~3.5 million Americans and 50 million globally, for which a Phase 1 study was initiated in 2H22 with data expected in 1H23. If successful, management expects to initiate at least one pivotal epilepsy trial in 2H23.

For the Kv7 platform, the company paid Knopp a total upfront consideration of $93.8 million, consisting of cash and legacy Biohaven stock. Knopp is also eligible to receive milestones of $887 million on BHV-7000 and mid-single digit to low teens royalties.

BHV-1100. In addition to Biohaven's neurological programs, it owns BHV-1100, an antibody recruiting molecule that is being studied in combination with autologous cytokine induced memory-like natural killer cells and immune globulin to target and kill multiple myeloma [MM] cells expressing the cell surface protein CD38. A Phase 1a/1b study initiated in 4Q21 and is expected to enroll 30 newly diagnosed MM patients.