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Alzheimer's Disease

Does Axovant Have Any Hope in Alzheimer’s?

Hey, remember Axovant? That’s the company that acquired a shelved Alzheimer’s candidate from GSK (intepirdine) and promptly went public in June of 2015 at what seemed a ridiculous valuation ($15/share, raising $315 million). People certainly made money on it, but jeez, the whole business really had a nasty look to it. The company’s stock hit $29 its first day, and if you bought in then, you’ve had plenty of time to regret it. By August it was at $11. It hasn’t spent much time above $15 since then, but you’d have to assume that most everyone who got it at the offering price is long gone, anyway. Perhaps they’re in Bermuda, the fizzing biotech incubator where Axovant is incorporated.

I bring them up because their Alzheimer’s candidate is a 5-HT6 antagonist, which is a mechanism that other companies have also been pursuing. Lundbeck has just annonced phase III results on their compound, idalopirdine, and they are not good. The drug missed its primary endpoint at both doses, and the secondary endpoints were identical to placebo. Axovant’s stock is taking a hit on the news, as well it might. But hey, Axovant has been through this before, because back in February, Pfizer announced that they’d stopped development on their own 5-HT6 compound in the area. Alzheimer’s disease maintains its status as a flaming incinerator of clinical hopes. Why, you have to wonder, would anyone hold Axovant’s stock in anticipation of their 5-HT6 results after two similar efforts have both failed?

15 comments on “Does Axovant Have Any Hope in Alzheimer’s?”

  1. Hap says:

    Because sometimes lottery tickets win (even expensive ones)? Because no one knows much about Alzheimer’s and so Axovant might get lucky? Because the rest of their portfolio is doing well and so they need to have something to reduce their taxes? Because someone needs to learn a lesson about fools and money?

    Those are the ones I can come up with.

  2. David says:

    But there is one trial of an Alzheimer’s drug that I am very much waiting for – based on a paper in Nature by University of Manchester, funded by the Alzheimer’s Institute. They claim that an already used drug – mefenamic acid (approved for use for menstrual pain) is effective at reversing Alzheimer’s in mice.

    ” A team led by Dr David Brough from The University of Manchester found that the anti-inflammatory drug completely reversed memory loss and brain inflammation in mice.”

    I am guessing that it should be able to jump directly to phase III trials, but am not entirely sure I understand how these things work.
    But again… maybe the press is not being accurate in their characterization of the paper (though I tried to read it and it seemed accurate to me.)

    1. Mark Thorson says:

      Except for the problem that mice don’t get Alzheimer’s. The mouse models express amyloid at levels far above that seen in any human brain.

    2. I hope that this mefenamic acid clinical study is supported by evidence that, at the clinical doses used, mefenamic acid engages a target in the brain. This is important for two reasons. First, to my knowledge, mefenamic acid does not go into the brain too well. Second, there were scores of drugs already tested in humans in the absence of any target engagement evidence and based just on high-profile publications about cured “AD” mice (resuling in an apparent success rate in the AD drug development of about 0.4%, according to Jeff Cummings’ 2014 review).

    3. Me says:

      Bexarotene anybody?

  3. David says:

    Yes – that is always the problem with trials in things other than humans, isn’t it? But still safety should already be known, so it is only a question of efficacy, if I understand things correctly. So *should* it be possible to jump directly to stage III trials?

    1. Anon says:

      “so it is only a question of efficacy, if I understand things correctly.”

      Just like the countless other drugs for AD that all failed – due to lack of efficacy.

      “So *should* it be possible to jump directly to stage III trials?”

      Indeed it is possible, but very unwise. The whole point of Phase 2 is to fail fast and cheap if you’re going to fail anyway, rather than in a huge and costly Phase 3 trial. Also it’s not wise to jump right into thousands of patients in case you pick up any safety issues, so better to see them in a smaller trial first

      1. MikeC says:

        Excepting trials that fail to generate meaningful results or cause immediate harm, is “fail fast and cheap” really an option with an Alzheimer’s drug trial?

      2. dave says:

        I agree with all the comments except the “the point of 2 is to fail fast”. Here we have a drug that has shown 100% effectiveness in mice with an analog of Alzheimer’s disease. It has been shown safe in humans (but for a problem that is not likely that it was used with people with Alzheimer’s). If the efficacy is good then a small study should show it, and presumably would not be that expensive.
        If the notes that there are NO analogues of Alzheimer’s in humans are correct, then it seems to me that the only alternative that makes sense is to start trying drugs that are already known safe.
        Surely anything that has a strong signal would already have been noted. So if one is looking for something with a strong signal, one should try out drugs that *would not typically be used on the elderly”.
        Something that is only used to treat menstrual pain would surely fit in this category.

  4. Dr CNS says:

    They still have two other phase 3 studies going on, expected to read out in 1Q17.
    Who knows…

  5. Chrispy says:

    Always looked like a pump-and-dump-for-chumps setup to me.

    I hope I am proven wrong.

  6. Ty says:

    Although I don’t believe they will be any different, I thought the whole point of Axovant was patient selection. Did Lundbeck and Pfizer trials use any genotyping for ApoE4 positive patients?

    1. Dr CNS says:

      I don’t have an answer for you…
      In any case, do you know of a link between ApoE4 and the 5-HT6 receptor?

  7. loupgarous says:

    Axovant stock, at this point, is like Confederate money. You hang on to it if you bought at any point above $11 because your original choice in investment wasn’t rational, but born of wild hope. And who knows, maybe Axovant will rise again….

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