OBJECTIVES : PCSK9i, evolocumab (Amgen) and alirocumab (Sanofi, Regeneron), reduce low-density lipoprotein-cholesterol (LDL-C) in patients with cardiovascular disease (CVD) or familial hypercholesterolemia (FH). We summarize HTAs by the Institute for Clinical and Economic Review (ICER; USA) and National Institute of Health and Care Excellence (NICE; England).

METHODS : Review of PCSK9i HTA publications from ICER and NICE to identify methods, outcomes, key decision drivers, and impact of decisions.

RESULTS : ICER assessed PCSK9i in 2015 using a model which has assessed CVD prevention approaches for over 30 years. NICE appraised evolocumab and alirocumab in 2016, using manufacturer developed models. ICER assessed PCSK9i as a drug class, using an average wholesale cost ($14,350(£9,531)/year) and assumed that reduced LDL-C would reduce CV deaths. Incremental cost-effectiveness ratios ranged from $274,000/QALY (CVD, intolerant to statins) to $334,000/QALY (heterozygous FH, high LDL-C despite high-intensity statin treatment). ICER reassessed evolocumab in 2017 using longer-term trial data showing reduced risk for some CV events but not CV death. The incremental cost-effectiveness ratio at wholesale cost ($14,523(£11,024)/year) was approximately $1.3million/QALY (CVD, high LDL-C despite statin treatment), increased from $302,000/QALY in 2015. NICE found evolocumab (£4,422.60($6,491.45)/year) and alirocumab (£4,383($5937.20)/year) to be cost-effective for subpopulations when price discounts were applied, recommending both for patients with high LDL-C despite maximal statin treatment/intolerance. Differences in pricing and comparators (NICE: ezetimibe + statin; ICER: statin) may have contributed to differences between ICER and NICE cost-effectiveness estimates.

CONCLUSIONS : The influence of ICER’s 2015 review on US payer perceptions is unclear, however barriers including exclusion from insurance plans, prior authorization, and unclear requirements for prior statin failures cause rejection of high proportions of PCSK9i prescriptions by US payers. The recent trial data and ICER reassessment may further negatively influence payers. Trial results not demonstrating reduction in CV deaths may impact NICE recommendations in scheduled PCSK9i reassessments during 2018.