Access to PCSK9 Inhibitors Still Restricted

From their president on down, physicians at the American College of Cardiology (ACC) 66^th Scientific Session had 2 reactions to the FOURIER trial results on Friday:

First, they’re pleased they have proof that evolocumab reduces the risk of cardiovascular events while driving down cholesterol levels. And second, they want to know if this means payers will stop giving them a hard time.

Leading cardiologists at ACC said it is not easy to get their patients access to evolocumab, one of 2 proprotein convertase subtilisn/kexin 9 (PCSK9) inhibitors. Evolocumab and its rival, alirocumab, work by targeting a protein that affects the way the liver processes low-density lipoprotein (LDL) cholesterol; the drugs can lower it by 60%.

ACC President Richard Chazal, MD, called getting payers to cover PCSK9 inhibitors a “war of attrition.” Cardiologist Sandra Lewis, MD, said she hoped the evidence from FOURIER, and a substudy called EBBINGHAUS that found the drug does not cause cognitive problems, would make it easier for her to get coverage for her patients.

Cardiologists eagerly awaited PCSK9 inhibitors when they were approved in the summer of 2015. FDA approved Sanofi-Regeneron’s alirocumab (Praluent) July 24, 2015, and Amgen’s evolocumab (Repatha) on August 27, 2015. But both drugs arrived with list prices above $14,000 a year, and payers and pharmacy benefit managers said from the start they would use strict protocols to control costs.

Data presented this weekend show they weren’t kidding.

Seth J. Baum, MD, of Preventive Cardiology and researchers from QuintilesIMS and Amgen authored an abstract presented Saturday that showed 83% of the initial PCSK9 inhibitor prescriptions were rejected. Another 26% were later approved on a second try, for an approval rate of 43%. The analysis looked at patient data for 44,234 prescriptions from the year following alirocumab’s approval. Amgen funded the study.¹

The data show that patients in Medicare have an easier time getting approved than those with commercial insurance; Medicare approved PCSK9 inhibitors 57% of the time, compared with a 30% approval rate for commercial payers. David J. Harrison, PhD, a researcher for Amgen and a co-author of the study, said one commercial payer is an “outlier” with higher-than-average approval rates, but he declined to name the payer.

Beyond that, the data are head-scratchers. A given rate of statin or ezetimibe use was no predictor of whether a prescription would be accepted or rejected. The same was true for patients with a history of antiplatelet therapy, which researchers used as a marker for artherosclerotic cardiovascular disease, the condition specifically included in the FDA label for the drug class.

Based on the data, most physicians seek PCSK9 inhibitors for patients who already have a complex medical history; the most common clinical feature of patients whose prescriptions were accepted—and those rejected—was that they took a high-intensity statin with ezetimibe.

The data also confirmed reports at ACC that a “middle group,” those who have tried a medium-intensity statin but not the highest-intensity, are being rejected in large numbers.

The data showed that while cardiologists had better luck getting the drugs approved than primary care physicians, they still wrote 41.9% of the prescriptions rejected by commercial payers and 42.1% of those rejected in Medicare. Harrison noted that compared with other specialists—such as those who treat diabetes—cardiologists may not be accustomed to such pushback from payers.

New drugs often hit roadblocks in the prior authorization process, but Harrison said he could not recall seeing a class having this much trouble—although he acknowledged he had not researched this question.

Roxana Mehran, MD, was among the cardiologists Friday who said the FOURIER results should launch a discussion to achieve consensus on 2 things: which patients should have access to PCKS9 inhibitors, and how low should clinicians try to push LDL cholesterol?

“We have robust evidence these drugs work, and the obstacles must be taken away from physicians,” she said.

Duke Researchers Reach Same Conclusions

Using a slightly larger data set from Symphony Health Solutions, researchers from Duke Clinical Research Institute came to the same conclusion: the overwhelmingly majority of initial prescriptions for PCSK9 inhibitors are rejected, patients with commercial coverage are rejected more often than those in Medicare, and cardiologists have more success than primary care physicians, but both have high rejection rates. Researchers led by Ann Marie Navar, MD, PhD, calculated the overall rejection rate at 79%.

Navar said early problems with prior authorization were not unexpected, but things haven’t improved. “We did see prescription volume was increasing to 6000 per month,” where it leveled off, she said. However, rather than seeing this jump in prescription volume translate into more approvals, the approval rate “actually declined,” she said.

Her presentation featured a slide showing that approval rates by payer varied from 33% to 75%, although the payers were not identified. This disparity suggests that rejections are not only for clinical reasons, Navar said. In the Symphony data set, 48% of prescriptions for patients with LDL cholesterol levels below 190 mg/dL were rejected, but so were 58% of the prescriptions for those with LDL cholesterol levels 190 mg/dl or higher.

“We do not know whether some of these rejections are clinical appropriate and, in fact, some of them are,” she said. “We suspect some of these factors are not due to clinical factors alone.”

References

1. Baum SJ, Chen CC, Rane PB, et al. Characteristics of patients approved and denied access in PCSK9i therapy by payers. Presented at the 66^th Scientific Session of the American College of Cardiology, Washington, DC, March 17-19, 2017. Abstract 1258-435.

2. Navar AM, Taylor BT, Flevitz E, et al. Early challenges for PCSK9 inhibitor prescriptions and patients: rejections and rates unfilled. Presented at the 66^th Scientific Session of the American College of Cardiology, Washington, DC. March 17-19, 2017. Abstract 415-08.