In a JAMA Viewpoint this week, Mayo Clinic researchers predict of a coming overuse of PCSK9 inhibitors, the newest treatment category for patients with uncontrolled high cholesterol.

On July 24, the FDA approved Sanofi and Regeneron’s Praluent (alirocumab) and on August 27, approved Amgen’s Repatha (evolocumab). In clinical trials including 2,476 patients with heterozygous familial hypercholesterolemia, or otherwise at risk for heart attack or stroke, patients exposed to alirocumab had an average reduction in LDL cholesterol from 36 to 29 percent. Those patients were also taking a maximum dose of a statin drug, the current first-line therapy.

Patients treated with Repatha had about 60 percent reduction in LDL cholesterol over 12 weeks in one of the trials, according to the FDA. Pfizer’s PCSK-9 (bococizumab) is in Phase III trials and data from those trials is expected to be reported next year.

The researchers made four predictions why overuse is on the horizon:

1. Physicians will manage statin intolerance by switching away from statins. Today, patients with any intolerance to statin is managed by switching to another statin drug. The authors believe that physicians will (wrongly) reject the entire class and switch to a PCSK9 inhibitor, where less conclusive safety data are available.

2. There will be a return to emphasizing LDL-C targets. In 2013, the American College of Cardiology and the American Heart Association issued new cholesterol guidelines, which focused on CVD risk reduction instead of LDL-C targets. Measuring LDL-C has previously been used as a surrogate marker for effective CVD risk reduction, but is an imperfect surrogate, the researchers say. Data on the link between reduced LDL-C and PCSK9 inhibitors is available now, but data affirming an associated reduction in CVD won’t be available for another couple of years. 

3. PCSK9 inhibitors will be prescribed for statin failure. Similar to the logic of its first prediction: when a statin fails, the next option should be to switch to another statin, not switch to a PCSK9 inhibitor.

4. PCSK9 inhibitors will be prescribed for non-adherence to statins. PCSK9 inhibitors are given subcutaneously every 2-4 weeks; statins are daily. It is reasonable to assume that Sanofi and Amgen would be promoting the adherence benefits of more convenient dosing.

“Clinicians can now prescribe medications from an exciting new class of cholesterol-lowering drugs, PCSK9 inhibitors…Although the drugs appear promising, the lack of sufficient evidence of benefit and safety of the agents and their price tag—280 times greater than the out-of-pocket cost for statins—urge caution in the use of PCSK-9 inhibitors,” the authors wrote. “The 4 predictions in this Viewpoint forecast a future in which clinicians will willingly abandon this caution and potentially decrease the value of patient care…the hope is that prudent clinicians and informed patients will prove these predictions wrong.”

Our Take: We dedicated a lot of virtual ink to this story because of its importance to policymakers, physician groups, health systems, ACOs, and payers. That is, just about everyone on the delivery side of  healthcare.

According to the CDC, 73.5 million adults—nearly one-third of adults in the US—have high LDL cholesterol. About 30% of adults with high cholesterol have their condition under control and less than half are even seeking treatment. Why this matters: people with high total cholesterol are at twice the risk for CVD as people with their cholesterol under control. Controlling CVD and managing cholesterol are of course priority quality metrics for ACOs (and others).

The Mayo researchers might as well have been writing the drug makers' marketing plan. As former pharma marketers, that’s what we would do: sell against the class of drugs, so when treatment failure or intolerance occurs, suggest a switch to another category. Bring back controlling LDL as your success measurements. Argue the case for improved adherence with twice monthly vs. remembering to take your meds once or twice a day.

Here’s the problem: in a recent Institute for Clinical and Economic Review (ICER) cost-effectiveness study, for the specific patient population these drugs are meant to treat, PCSK9 inhibitors would have to cost about $2,400 per year. The two approved drugs average price is around $14,300 per year. In comparison, generic atorvastatin (Lipitor) costs around $13/month, about $150/year.

NET AVERAGE ANNUAL COSTS

Source: Institute for Clinical and Economic Review

The non-profit, independent ICER warned of the staggering cost increases on the horizon. Including cost offsets due to reduced cardiovascular events, ICER estimates $7.2 billion in year one. Over five years, the estimate climbs to an annualized $21.4 billion per year in net healthcare cost growth. That figure accounts for, we repeat, costs that are offset by reduced CVD.

We have our own prediction. Policymakers and providers will be watching this category closely in the coming months, especially when the marketing muscle of Pfizer is on the street.

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