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.