Cost-effectiveness of Evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease

Importance: The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data. Objective: To evaluate the cost-effectiveness of evolocumab in patients with atherosclerotic cardiovascular disease when added to standard background therapy. Design, Setting, and Participants: A Markov cohort state-transition model was used, integrating US population-specific demographics, risk factors, background therapy, and event rates along with trial-based event risk reduction. Costs, including price of drug, utilities, and transitional probabilities, were included from published sources. Exposures: Addition of evolocumab to standard background therapy including statins. Main Outcomes and Measures: Cardiovascular events including myocardial infarction, ischemic stroke and cardiovascular death, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and net value-based price. Results: In the base case, using US clinical practice patients with atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol levels of at least 70 mg/dL (to convert to millimoles per liter, multiply by 0.0259) and an annual events rate of 6.4 per 100 patient-years, evolocumab was associated with increased cost and improved QALY: incremental cost, $105 398; incremental QALY, 0.39, with an ICER of$268 637 per QALY gained ($165 689 with discounted price of$10 311 based on mean rebate of 29% for branded pharmaceuticals). Sensitivity and scenario analyses demonstrated ICERs ranging from $100 193 to$488 642 per QALY, with ICER of $413 579 per QALY for trial patient characteristics and event rate of 4.2 per 100 patient-years ($270 192 with discounted price of $10 311) and$483 800 if no cardiovascular mortality reduction emerges. Evolocumab treatment exceeded $150 000 per QALY in most scenarios but would meet this threshold at an annual net price of$9669 ($6780 for the trial participants) or with the discounted net price of$10 311 in patients with low-density lipoprotein cholesterol levels of at least 80 mg/dL. Conclusions and Relevance: At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of$150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and$6780 for trial participants), or a higher-risk population would need to be treated

Pooled safety analysis of evolocumab in over 6000 patients from double-blind and open-label extension studies

Background—Evolocumab, a fully human monoclonal antibody to PCSK9, markedly reduces LDL-C across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group. Methods—This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in two OLE trials. Adverse events were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs (SAEs), laboratory assessments, and AEs of interest were evaluated. Results—Overall AE rates were similar between evolocumab and control in the parent trials (51.1% vs 49.6%) and in Year 1 of OLE trials (70.0% vs 66.0%), as were those for SAEs. Elevations of serum transaminases, bilirubin and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive adverse events were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups vs 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing anti-evolocumab antibodies were detected. Conclusions—Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in open-label extension trials for 1 year supports a favorable benefit-risk profile for evolocumab

Pooled safety analysis of evolocumab in over 6000 patients from double-blind and open-label extension studies

Background—Evolocumab, a fully human monoclonal antibody to PCSK9, markedly reduces LDL-C across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group. Methods—This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in two OLE trials. Adverse events were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs (SAEs), laboratory assessments, and AEs of interest were evaluated. Results—Overall AE rates were similar between evolocumab and control in the parent trials (51.1% vs 49.6%) and in Year 1 of OLE trials (70.0% vs 66.0%), as were those for SAEs. Elevations of serum transaminases, bilirubin and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive adverse events were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups vs 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing anti-evolocumab antibodies were detected. Conclusions—Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in open-label extension trials for 1 year supports a favorable benefit-risk profile for evolocumab