We are potentially on the brink of another massive leap forward in terms of cardiovascular (CV) disease prevention. The first of the late-breaking trials to be presented at ACC.17, highlighting its importance, is FOURIER, the CV outcomes trial for Amgen’s PCSK9 inhibitor Repatha (evolocumab). These data will hopefully show that the additional LDL-cholesterol lowering efficacy from PCSK9 inhibition translates into real CV benefits.

Of course, Amgen has already announced that the trial is positive – so no break here. But will the results make the drug? The consensus among thought leaders is that a 20% reduction in the primary endpoint is the benchmark: exceed this threshold and Repatha becomes a clinical game changer. If we discount the modest impact demonstrated for ezetimibe in the IMPROVE-IT trial, these data could show the first substantial improvement in CV outcomes since the seminal statin outcomes trials. On the back of these trials, simvastatin (Merck’s Zocor), atorvastatin (Pfizer’s Lipitor), and rosuvastatin (AstraZeneca/Shionogi’s Crestor) all reached peak annual sales in excess of $5 billion. However, the statins emerged as first-line therapies in a therapeutic space that was calling out for novel drugs, Moreover, they are oral therapies that do not cost the earth. In contrast, Repatha and its chief competitor Sanofi/Regenon Pharmaceuticals’ Praluent (alirocumab) are very expensive injectable biologics that must contend with much less expensive generic statins and ezetimibe.

To date, uptake of PCSK9 inhibitors has been slow. This is in part due to the limited pool of patients that need additional LDL-cholesterol-lowering treatment on top of statin and ezetimibe. Repatha’s current FDA label specifies that the drug is indicated on top of statin therapy for familial hypercholesterolemia (HeFH) or clinical atherosclerotic CV disease (ASCVD) who require additional LDL-cholesterol lowering. But by including patients with ASCVD and an LDL-cholesterol level of ≥ 70 mg/dL who are at high risk of a recurrent CV event, it potentially opens up almost the whole secondary prevention population, which in the United States alone is tens of millions of patients. However, most experts in the field of CV prevention believe that these agents are only required for those patients at the highest CV risk. But how will physicians at the bedside interpret ‘high risk’ of a recurrent CV event?

Clinical definitions and label criteria aside, the real stumbling block for PCSK9 inhibitors is the cost. At an annual U.S. price of more than $14,000, payers have placed several cost controls to restrict access to these novel agents. If Repatha receives an expanded label to treat almost all ASCVD patients, the impact on healthcare budgets would be prohibitive. Even with positive CV benefits, proving the cost-effectiveness of PCSK9 inhibitors to payers will be challenging. Payers are going to need to be convinced that not only do these drugs save lives and prevent CV disease, that they will bring costs down in the long term. Economic studies for and against have already been produced, so the waters remain muddy, which may allow payers to maintain strict cost controls and limit access to only those at very high risk for recurrent CV events.

All in all, we expect Repatha to make a clinically meaningful impact for patients with ASCVD, break the blockbuster sales barrier, but still cause too much of an economic ache for payers to permit widespread use.

Click here for an overview of some of the other exciting new research on dyslipidemia treatments being presented at ACC.17.

For DRG’s analysis of the Dyslipidemia market, please click here.

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