So an FDA advisory committee met yesterday to consider the PCSK9 antibody from Regeneron and Sanofi, and today it’s the turn of Amgen’s candidate. These, as anyone with even a passing interest in cardiovascular medicine will know, are potential gigantic blockbusters and advances in the field, promising to lower LDL across a huge swath of the patient population. The question, though, is clinical outcomes – the big question is always clinical outcomes. Does lowering LDL via this mechanism lead to lower CV mortality, fewer heart attacks, etc.? By now, we have such data for statin therapy, and it does indeed seem to provide those benefits. Those numbers take years to generate, though, and although these studies are underway, the various PCSK9 developers would much rather not wait another two or three years for them to report, in much the same way that you or I would rather not spend that time dangling by our feet. So everyone is looking for a way to get these drugs onto the market.
Sanofi and Regeneron are looking to target patients who have a genetic predisposition to high LDL levels, and a larger group who are intolerant to statin therapy. The FDA committee was fine with the first plan, but not wildly enthusiastic about the second one. One worry they seemed to have was sending a “ditch your statins” message, which they don’t want to do.
A whole generation of well-known statins, now cheap and easily available, has emerged with proven cardiovascular benefits for patients. Other LDL drugs, though, turned out to be controversial failures on CV outcomes. The FDA is fretting that an approval based on the LDL surrogate leaves it with no authority to demand a cardiovascular study. And regulators are alarmed over the impact these new drugs could have on statins, even though there are no proven CV advantages.
That’s from this FierceBiotech piece, written before the committee meeting. Here’s their take afterwards. Matthew Herper has an analyst who thinks that many statin-intolerant patients will go onto the new therapies, no matter what the label might way. We’ll see. No PCSK9 antibody is going to reach its full market potential until the outcomes data arrive – that much has been clear for a long time. But now the companies (and their investors) are wondering about what they’ll be able to realize before that happens.