The availability of a specialty drug doesn’t guarantee its accessibility, as cardiologists who try to prescribe PCSK9 inhibitors to their patients are learning. Insurers’ requirements for prior authorizations can create formidable barriers, but some providers have found ways to surmount them.
Huge efforts, small rewards
The juxtaposition likely galled many cardiologists. The FOURIER study, one of ACC.17’s late-breaking clinical trials, showed the clear benefit of a PCSK9 inhibitor for treating some patients with atherosclerotic cardiovascular disease (N Engl J Med 2017;376[18]:1713-22). Meanwhile, a team from the Duke Clinical Research Institute in Durham, N.C., reported that more than half of PCSK9 inhibitor prescriptions were rejected by pharmacy benefit managers, and among those approved, more than a third went unfilled.
Compared with a placebo, patients in FOURIER who received evolocumab (Repatha, Amgen) and statin therapy overall saw their low-density lipoprotein (LDL) cholesterol drop a median of 59 percent, with a 15 percent reduced risk of a composite of heart attack, stroke, hospitalization for angina, revascularization or cardiovascular death. Evolocumab and another PCSK9 inhibitor, alirocumab (Praluent, Sanofi-Aventis), both received FDA approval in the summer of 2015 as a treatment for patients with familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease.
The drugs, injectable monoclonal antibodies that target LDL receptors, are pricey, at a list cost of about $14,000 annually. That qualifies them as specialty medications, a category that requires physicians and patients to obtain prior authorization. With PCSK9 inhibitors, that can be a challenge.
“Various pharmacy benefit managers have different and sometimes unclear criteria for what they call hypercholesterolemia, the criteria for when they would approve the medication, the documentation required, the use of other medications and current labs,” says Joshua W. Knowles, MD, PhD, a cardiologist at Stanford University Medical Center in California and chief medical adviser for the FH Foundation in Pasadena.
Knowles participates in FH Optimal Care of the United States (FOCUS), a study designed by the FH Foundation to assess treatment patterns for patients with FH. FOCUS taps into a larger dataset that includes more than 140 million cases of treated or investigated cardiovascular disease and related prescription data, according to Kelly D. Myers, the foundation’s chief technology officer and a FOCUS investigator.
In one analysis, they identified 237 patients with presumed FH and 1,622 patients with established atherosclerotic cardiovascular disease whose LDL cholesterol levels and lipid-lowering treatments met the indications for PCSK9 inhibitors (Circulation 2017;135[22]:2204-6). The PCSK9 inhibitor rejection rates for the FH and the atherosclerotic cardiovascular disease cohorts were 63.3 percent and 57.5 percent, respectively. The lag between submission and approval exceeded two months in 40 percent of the prescriptions.
“Of those with paid prescriptions, most had an average of two or three rejections ahead of paid prescription,” Myers says. “I think the record in the data was seven before they ended up on paid medications. This was all in the first year on the market, so I am sure that record has been broken by now. Persistence is very much a part of the theme here.”
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“The biggest problem is that it is labor intensive and time consuming for the office and there is no reimbursement for it,” Ballantyne says. And to boot: “After a year you have to do it over again, the whole process.”
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Pathway to prescription approvals
Ballantyne and the team at Baylor created a pathway for PCSK9 inhibitor prior authorizations in an effort to save time and increase the likelihood of approvals. The protocol borrowed from a 2016 expert consensus document that Ballantyne helped write that provided a decision pathway for prescribing non-statin, lipid-lowering therapies (J Am Coll Cardiol 2016;68[1]:92-125).
They tailored the protocol specifically for PCSK9 inhibitors in a flowchart that helps providers identify eligible patients, facilitate the prior authorization process and speed up approval. They also formalized the patient education component and noted that more than half of eligible patients chose not to go forward with the treatment after those discussions. In the first year of using the pathway, they obtained authorization for 17 eligible patients upon first request and an additional six patients after one appeal (J Clin Lipidol 2017;11:596-9).
“You really want to make sure the patient meets the criteria of having either credible atherosclerotic cardiovascular disease or familial hypercholesterolemia and is on a maximally tolerated statin,” Ballantyne says. The flowchart is designed to ensure payers’ see all of their requirements have been met. “We have a checklist and, if you don’t have all the boxes checked, you will be denied.”
Knowles emphasizes that physicians must understand they can’t stray from the drug’s indication: for alirocumab, atherosclerotic cardiovascular disease or heterozygous FH; and for evolocumab, those two plus homozygous FH. They also must document that the patient was on a maximally tolerated statin and did not achieve the desired LDL cholesterol levels.
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“It is important to note that most FH patients will not require these medications,” Knowles says. His first strategy is to try other lipid-lowering medications before moving on to a PCSK9 inhibitor. He accompanies a PCSK9 inhibitor request with careful documentation to establish why he thinks the patient qualifies, including family history, personal history, physical characteristics and results from genetic testing, if available. He uses an app to calculate the possibility of FH and associated risks. “When you calculate those things, it is hard for a medication to be denied.”
The FH Foundation also tries to educate patients and payers to improve access to the drug. For instance, the nonprofit encourages patients with a denial to coordinate with their providers to make a case for approval, whether calling as a customer or by writing a letter. “We have a guide for patients to understand the whole process, prior authorization and appeals and what role they can play,” says Katherine A. Wilemon, the foundation’s founder and CEO.
This spring, the nonprofit worked with the pharmacy benefit manager Express Scripts to make its diagnostic criteria more comprehensive, widening the potential pool of people with the disorder who could benefit from treatment. The plan is to present evidence from the FOCUS study to payers and pharmacy benefit managers in an effort to eliminate other barriers to access.
Cost considerations
Payers may have legitimate reasons for trying to rein in the use of PCSK9 inhibitors. Ballantyne and colleagues calculated if the FOURIER entry criteria were applied to Veteran Affairs patients with atherosclerotic cardiovascular disease, about a fourth of the veterans would qualify at a cost of more than $2 billion a year (Circulation 2017;135[25]:2572-4). Yet half of those eligible patients would not be taking high-intensity statins; increasing the use of high-intensity statins and ezetimibe would cut costs by about $1 billion annually.
If their high cost puts PCSK9 inhibitors in payers’ cross hairs, they also pose a barrier for patients facing co-pays that may reach $400 a month. Myers noted that in FOCUS a higher proportion of abandoned prescriptions had high co-payments compared with no co-payments.
“Anecdotally, the biggest barriers are cost and then risk–benefit analysis by the patient,” Knowles says. “Remember that FH is a silent killer in that you are not in pain from FH unless you have a heart attack or something like that. Convincing people to take their medicine for prevention and maybe having high out-of-pocket cost for that is a challenge.”
Earlier preventive care might obviate the need for PCSK9 inhibitors, says Wilemon. While the foundation advocates for payers and pharmacy benefit managers to make the prior authorization process for PCSK9 inhibitors less arduous and more inclusive for appropriate patients, it would rather see patients never reach that stage in the first place.
The foundation estimates that 13 million people in the U.S. have FH, but only 10 percent are diagnosed with the genetic disorder. “We would like to get people diagnosed much earlier and treated with first-line statin therapy to prevent the progression of heart disease and hopefully many of them will do quite well with first-line therapy,” she says. “That is the best-case scenario.”