PCSK9 drugs show viability, tolerability

Amgen and Sanofi report PCSK9 results
Amgen and Sanofi report PCSK9 results

New clinical data shows that Amgen and Sanofi and Regeneron have viable cholesterol-lowering PCSK9 inhibitors, but that data also indicates that marketers will have to work hard to differentiate the two drugs when and if they hit the market.

The results for Amgen's Repatha (evolocumab) and Sanofi/Regeneron's Praluent (alirocumab) were released at the American College of Cardiology's annual meeting in San Diego on Sunday. The drugs are facing regulatory reviews this year: The FDA has until July 24 to approve or reject Sanofi/Regeneron's Praluent and until August 27 to weigh in on Amgen's Repatha.

Both monoclonal antibodies were associated with lowering LDL levels—the bad cholesterol levels—by around 60%. “It's very promising,” Dr. Jennifer Robinson, lead researcher on the Sanofi/Regeneron study and co-author of Amgen's study, told MM&M, adding that “what it really tells us is that we are on the right track … the reason we lower LDL is to lower heart attack and stroke, so it looks like a positive signal in that regard.”

The drugs are primarily being considered for patients with the genetic condition familial hypercholesterolemia, which prevents the body from removing LDL cholesterol from the blood and therefore puts them at risk for early-age atherosclerosis. PCSK9 inhibitors are also considered an alternative for patients who cannot tolerate statins.

These studies were not designed to assess the drugs' impact on heart attack and stroke, but the data, which was compiled to support lowering LDL, indicated that the drugs could halve the risk of heart attack. Leerink Partners analyst Seamus Fernandez wrote in a Sunday research note that he had expected some cardiovascular risk reduction but not of this magnitude.

Robinson told MM&M that the clinical trial findings have an additional benefit: “It appears that these PCSK9s are really truly well tolerated.” Common side effects included reactions at the injection sites and joint pain.

Sanofi and Regeneron deployed an unbranded marketing push in December, with the launch of their “Cholesterol Counts” campaign. The goal was to encourage Americans to think about cholesterol, as well as to provide poll partners, like the National Lipid Association, with an idea of what the public does and does not know about cholesterol and if they talk to their doctors about their LDL levels.

Pharmacy benefits managers have also started to prepare for the arrival of these drugs in the marketplace.

CVS Health estimated in last month's Health Affairs that a year's treatment of these new drugs could cost between $7,000 and $12,000. The CVS execs said this annual total could represent a $16.4-billion market if the focus is limited to the 620,000 American familial hypercholesterolemia patients. They wrote that applying these drugs to the 3.2 million patients who are statin-intolerant or who have a poor satin response could boost this number to between $50 billion and $100 billion.

At least two other drugmakers are developing PCSK9 inhibitors so the results bode well for the class as a whole, Fernandez wrote. Pfizer's pipeline includes bococizumab and Eli Lilly's PCSK9 program includes LY3015014.

Widespread PCSK9 drug use has a way to go. First, an approval needs to happen. Second, both Amgen and Sanofi/Regeneron are initially seeking an LDL-lowering indication, as opposed to one that includes heart-attack prevention.

Robinson said things will progress one step at a time. She also said that these new drugs may not supplant statins. She said these older medications, which she called “miracle drugs in a way,” have a history of reducing cardiovascular events, and that their generic, generally cheap status makes them “a good bargain.”