PCSK9 inhibitor approvals provide LDL cholesterol-lowering options

As expected, the FDA approved evolocumab (Repatha) on Aug. 27, providing an option for patients who struggle to lower their low-density lipoprotein (LDL) cholesterol with statins. In July, the FDA had approved alirocumab (Praluent), which like evolocumab is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor.

Despite clinical trial evidence showing both PCSK9 inhibitors significantly reduce LDL cholesterol, concerns have been raised about their high costs. The annual wholesale acquisition cost is $14,600 for alirocumab and $14,100 for evolocumab. Both drugs are injectable medications taken every two weeks or monthly.

On Sept. 8, the nonprofit Institute for Clinical and Economic Review (ICER) is scheduled to release a report for public comment on the clinical effectiveness and long-term economic value of the PCSK9 inhibitors.

Since the spring, clinicians, clinical epidemiologists, health economists, physicians and others have been working on the ICER report, which should provide patients, payers and healthcare professionals a better understanding of alirocumab and evolocumab.

“One of the key questions has been what’s the role in therapy of these drugs?,” Steven D. Pearson, MD, the founder and president of ICER, told Cardiovascular Business in July. “The FDA emphasized there are some patients who have a genetic predisposition to extremely high cholesterol levels and even if they take the highest-dose statin they may not have their cholesterol come down as far as the doctors would like. There is a much larger group that’s had a cardiac event such as a heart attack or stroke who may be on statins or have trouble with statins.”

Pearson added: “There are still lots of questions about larger patient groups. Most of the time, people are talking about adding this drug to statins, but there are a large number of patients who aren’t on statins for one reason or another. How those patients will be managed is going to be an important question.”

The drugs have also not been proven to prevent or delay MI, ischemic stroke and death due to cardiovascular disease, although ongoing outcomes studies are evaluating those end points.

Peter Wilson, MD, an FDA advisory committee member who did not vote for the approval of either PCSK9 inhibitor, expressed concern that both drugs are on the market too soon.

“We don’t have outcomes; it’s hard to recommend approval without outcomes,” Wilson told Cardiovascular Business in June. “I’m on the conservative side of assessing these types of new molecules. We have a pretty good portfolio of lipid medications… I’m data driven, and especially when we have expensive new products, we’ve got to be data driven. We cannot just be anecdotal because once we’re there, the products get overprescribed and we don’t even really know how much benefit we’re getting out of these.”

-Tim Casey
Executive Editor - Cardiovascular Business