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What a Brief Regeneron Panic Tells Us

Matthew Herper has a good article on a recent (and fortunately short) scare for Regeneron. Several investors had used the Freedom of Information Act to get FDA adverse-event reporting on the PCSK9 drugs, and this made it look as if Regeneron’s Praluent (alirocumab) was associated with several suicides, while Amgen’s Repatha (evolocumab) wasn’t. Now that would be bad news, terrible news, but it wasn’t so. Basically, the quality of the data in the system was very poor – there was one suicide, in an individual with a pronounced history of chronic depression, and for some reason it got reported six times. Another reported suicide seems to have been from a patient who never received the drug at all. The FDA itself came out with a statement trying to clear all this up.

Now this doesn’t mean that there are (or will be) no problems with Praluent (or with Repatha). They’re drugs that work by a mechanism that’s never been tried in humans, and you always have to be on the alert. It’s true that there are some people with natural loss-of-function mutations in PCSK9, who seem fine – in fact, it was their favorable lipid profiles that put the world onto this as a drug target in the first place. But a knockout-from-conception organism can be quite different than a pharmacological knockdown in an adult, as has been proven many a time. All sorts of compensations can take place during development that aren’t always available to a fully grown mouse, rat, or human. But (on the infamous other hand) there are plenty of these things that translate just fine, too. There’s literally only one way to find out, and that’s what we’re doing right now.

Another point that needs to be made about all this is how easy it is to misinterpret raw data. That’s one of my main complaints with some of the right-to-try proposals, or the general FDA-should-get-out-of-the-way crowd. I’m not saying that there’s not such thing as regulatory burden, or that it can’t be taken too far. But it’s important to realize that dealing with clinical data and field reports from patients is a lot harder than it looks. Even when the numbers are solid, they need a lot of careful handling, and sometimes they’re just sheer junk to start with, even though the two may look (at first) indistinguishable. There’s a very real risk of coming to the wrong conclusion, especially if you’re trying to work quickly, and going into Headless Poultry Mode.

For now, the real question about the PCSK9 drugs is how many people are taking them. Physicians may be wondering about long-term outcomes, and that’s not a silly question at all, considering how complicated lipidology is. They’re not cheap, to put it mildly, which prices them as if the benefits are going to be exactly as hoped for. And while that may be true, it’s too early to say for sure.

7 comments on “What a Brief Regeneron Panic Tells Us”

  1. Anon says:

    “there was one suicide, in an individual with a pronounced history of chronic depression, and for some reason it got reported six times”

    Better 6 than none. That’s actually quite comforting.

  2. CMCguy says:

    Herper has a good statement in his piece “The lesson: A little data can be a dangerous thing. Often, what looks like information in medicine is just noise. But, from a stock perspective, things get more complicated.” One of the reason Drug Develop is so darn hard is being able to differentiate any real responses from the noise, especially in individual patients where there may be contributory issues (such as suggest mental health history in this case). I do believe there needs to be greater transparency and publication of clinical trial results however without allowance for full context or rational analysis it is very easy to misinterpret or worse tailor conclusions. While scientists are not immune or often without agendas if they hold to objective standards methods I tend trust their results much more than “investors” and also lawyers where the facts get obscured to support what they want the meaning to be. Herper did not mention but I wonder if any SEC action might occur for stock manipulation by the investors?

  3. Anon 2 says:

    ^ Welcome to the era of “accidentally on purpose” manipulating stocks by “accidentally on purpose” getting a third party to “accidentally on purpose” spread fear by “accidentally on purpose” misinterpreting raw data.

    Why create value when you can just take it from others? Sad, sad world we live in.

  4. Barry says:

    the experiment of nature that has not yet been realized as a therapeutic is ApoA-1 Milano. Just as humans with mutant PCSK9 have better than normal circulating lipid profiles, so with ApoA-1 Milano. The first trial in humans showed dramatic regression of arterial plaques. But since then, no one has managed to bring this out as a therapeutic.

  5. watcher says:

    This is the type of downside to when anyone can get access to bits of information that is incomplete, and they are not qualified to analyze or interpret. Unfortunately, this unsubstantiated and non-valid statement will now continue forever on the internet to continually raise questions about the drug’s safety.

  6. John says:

    I didn’t know these were monoclonal antibodies until I clicked the links. I could hear my insurance company shrieking already.

    1. John Harrold says:

      If it ends in mab then it’s a mab 🙂

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