PCSK9 Inhibitors and Specialty Pharmacy

Results from research show that nearly 30% of Americans 40 years and older use a prescription medication to control their cholesterol and that 83% of that population use statins. However, many patients, specifically those with familial hypercholesterolemia, are unable to adequately reduce low-density lipoprotein cholesterol (LDL-C) with maximal doses of statins. As such, the use of alternative cholesterol-lowering agents is necessary for patients with uncontrolled LDL-C levels, according to the continuing education (CE) session “Managing Hypercholesterolemia: Clinical Updates for Specialty Pharmacists on PCSK9 Inhibitor Therapy,” presented at the Asembia Specialty Pharmacy Summit 2018.

Although older statin alternatives have shown modest efficacy in lowering LDL-C levels, the FDA approvals in 2015 of the first 2 PCSK9 inhibitors signaled a change in the treatment landscape for high cholesterol. The CE session, presented by Sheena Babin, PharmD, pharmacy clinical services and business development manager at Ochsner Specialty Pharmacy, and Joseph J. Saseen, PharmD, FCCP, FASHP, BCPS, BCACP, professor of clinical pharmacy and family medicine and vice chair for the Department of Clinical Pharmacy at the University of Colorado, detailed to the specialty pharmacy audience the importance of being able to identify patients for whom PCSK9 therapy could be appropriate and of providing patients and physicians with accurate information regarding dyslipidemia and treatment with PCSK9 inhibitors.

Cardiovascular disease ranks as the leading cause of morbidity and mortality in the United States, and individuals with high cholesterol have twice the risk of developing heart disease as people with lower levels. Meanwhile, approximately 71 million Americans have high LDL-C, of whom only one-third have their levels under control and less than half receive treatment.

The first 2 agents to gain approval in the PCSK9 inhibitor class—alirocumab (Praluent) and evolocumab (Repatha)—are currently indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Evolocumab is also approved as an adjunct to other LDL-C—lowering therapies in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C. A third PCSK9 inhibitor, bococizumab, is currently being evaluated in phase 3 trials.

Alirocumab and evolocumab are both monocloncal antibodies administered via subcutaneous injection to prevent PCSK9 from degrading hepatic LDL receptors, thereby increasing the number of receptors, and, in turn, clearing more LDL from circulation. In a pair of trials—ODYSSEY and FOURIER—the PCSK9 inhibitors were found to be effective in improving cardiovascular outcomes.

In the ODYSSEY trial, alirocumab was found to improve cardiovascular outcomes and reduce all-cause deaths by 15% in patients with acute coronary syndrome and higher-than-ideal atherogenic lipoprotein levels despite intensive or maximally tolerated statin therapy.

The trial randomized 18,924 patients to receive either subcutaneous injections of alirocumab 75 mg every 2 weeks or placebo, with both groups given a target LDL level of 25 to 50 mg/dL. At a median follow-up of 2.8 years, LDL-C level was 53.3 mg/dL in the alirocumab cohort, compared with 101.4 mg/dL in the pla- cebo cohort (54.7%). Furthermore, the duration to occurrence of coronary heart disease death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or ischemic stroke was 9.5% in the alirocumab group, compared with 11.1% in the placebo group.

In the FOURIER trial, the efficacy and safety of evolocumab were evaluated among individuals who had an elevated cardiovascular risk and who were on statin therapy. The trial randomized 27,564 patients with established cardiovascular disease on statin therapy to receive evolocumab 140 mg subcutaneous every 2 weeks or 420 mg monthly versus placebo every 2 weeks. Incidence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization was observed in 12.6% of the evolocumab cohort, compared with 14.6% of the placebo cohort. Evolocumab was also found to significantly reduce LDL-C levels.

With the currently approved indications for alirocumab and evolocumab, Express Scripts estimated that 5 million to 10 million patients may be eligible for treatment. As a result, limits on insurance coverage for PCSK9 inhibitors have proved to be a significant hurdle for patients seeking to use these agents. The prior authorization process has been found difficult, specifically for cardiology clinics not familiar with prescribing specialty medications. Consequently, specialty pharmacists are useful in helping patients gain access to PCSK9 inhibitors. As such, educating specialty pharmacists on strategies to document a patient’s need for these drugs and in appealing insurance coverage denials is vital.