So, PCSK9. A wonderful story of genetics-based drug discovery, and a huge commercial opportunity. People with loss-of-function PCSK9 genes have very low LDL cholesterol, with no other ill effects, and people with gain-of-function mutations have chronically high cholesterol. That’s about as good as the validation gets, so a number of drug companies have gone charging after the target over the last ten to fifteen years.
The two big players, with antibody-based drugs on the market, are Regeneron/Sanofi and Amgen (and they’re all currently fighting it out in court). But the drugs themselves are not the gigantic blockbusters that some had predicted by this point, mainly because everyone’s been waiting for real cardiovascular outcomes data. Insurance companies are turning down prescriptions in favor of much cheaper and far better proven statin therapy, which also lowers LDL, until they can be sure that PCSK9 is worth the steep price. Sure, you can lower LDL by taking the PCSK9 drugs – but does that really translate into lower death rates from cardiovascular events? It should, according to what most people think about LDL and heart disease, but does it really?
This morning we have three-year data from Amgen and their drug Repatha (evolocumab), an announcement that has been eagerly awaited. And it’s honestly not all that impressive. There’s a 15% relative reduction in cardiovascular risk (heart attack, stroke, etc.) relative to placebo, but investors were looking for something more over 20%. Insurance companies were probably looking for that, too, and given the price they’d have been happier to see something more like 25%. Amgen is defending the data (as quotes in this Adam Feuerstein piece show), but I don’t think that’s going to do the job. The numbers shouldn’t have to be interpreted and spun; in a three-year study with over 13,000 patients in each arm, the numbers should be able to speak for themselves, and they don’t.
Keep in mind that these are numbers relative to placebo, too – ;what would a head-to-head trial versus a generic statin show? Update: the control arm was indeed on high-dise statin therapy. Is there enough difference to justify the $14,000 list price for Repatha (or for the similarly priced Regeneron/Sanofi drug?) I have to doubt it. Look for everyone in this space to take a hit in the stock market today, and for insurance companies to continue turning down prescriptions.
Update: in a follow-up post, I’ll have more thoughts on what this means for the gene-to-drug philosophy that PCSK9 has been a key example for. . .