Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy

Abstract

Background PCSK9 inhibitors (PCSK9i) are a novel class of medications for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) requiring additional lipid lowering beyond dietary measures and statin use. Because of the drugs' high cost, rates of prescription approval by payers may be low. We aimed to identify payer approval and rejection rates for PCSK9i prescriptions, and potential factors influencing these rates. Methods This is a retrospective, descriptive cohort study utilizing nationwide pharmacy claims linked to electronic medical records from a nationwide data warehouse. The dataset includes over 220 million patients from all fifty states and all payer types with 5,140 distinct health plans. PCSK9i prescriptions were submitted for 51,422 patients in the pharmacy dataset. The main outcome was approval or rejection of PCSK9i prescription claims. Factors associated with approval and rejection of these medications in the US were assessed. Results Among patients who were prescribed a PCSK9i, 47.0% were approved for coverage by the payer. Variables that were associated with PCSK9i approval included age >65 years (p<0.01), history of ASCVD (p<0.01) prescription by a cardiologist or non-primary care provider (p<0.01), statin intolerance (p=0.03), longer statin duration (p=0.01), and non-commercial payers (p<0.01). Higher low density lipoprotein cholesterol (LDL-C) levels were not associated with higher approval rates. Commercial third-party payers had the lowest approval rates (24.4%) and Medicare had the highest (60.9%). Conclusions Rates of approval for PCSK9i therapy are low, even for patients who appear to meet labeled indications. While a combination of clinical characteristics increases the likelihood of approval, payer type is the most significant factor.

Application of PCSK9 Inhibitors in Practice

“…Overall, the implementation of a dedicated PCSK9i clinic has resulted in a 97% rate of drug approval, far higher than the national average approval rate of 40–50% reported in the literature. 9–12 Financial burden for patients was very reasonable in most cases, with an average monthly out-of-pocket expenditure of $57 and discontinuation rates due to cost of only 2.3%. This high approval rate and low patient out-of-pocket expenditure stands in contrast with media reports and the peer-reviewed literature in which about a third of patients were reported never filling PCSK9i prescriptions primarily due to cost.…”

“…Prior reports of PCSK9i treatment have provided details from either the clinical trial perspective, 4–6 the provider perspective, 7–12 or the payer and societal perspectives. 13–18 However, few reports have reflected the patient experience with PCSK9i in clinical use.…”

Precision Medicine and Big Data

“…Uptake of PCKS9 inhibitors, however, has been marred by its high cost-currently between USD 5000 and USD 14,000 per year of treatment, which may last for the rest of the patient's life. This has been shown to be not cost-effective (Korman et al 2018), and many insurers decline to cover it (Hess et al 2017). Access, then, will depend in large part on the ability of patients to afford the high out-of-pocket costs of the treatment.…”

Elephant in the Room

“…A high-burden PA process may be related to high rates of rejection for submitted PCSK9i prescriptions because other studies have reported that commercial payers also had the lowest PA approval rates. 2,3 Why are we examining the intricate details of the PCSK9i PA process and high rejection rates? The reason is clear-simply put, these drugs are expensive and at a level not previously seen for a drug with this potentially large of a market.…”

“…In evaluations of current populations that might be eligible for PCSK9i, more than half of eligible patients were not receiving statin therapy, which clearly represents a deficiency in optimal risk reduction management. 2,3 Oftentimes, excitement surrounding the uptake of new drugs drives potential overuse, even in the absence of outcomes evidence, with subsequent difficulty with reining in prescribing in all but the strictest of formularies. 8 Abandonment of existing effective therapies may also ensue, and this seems to be the case with the excitement surrounding PCSK9i.…”