Early health technology assessment of gene silencing therapies for lowering lipoprotein(a) in the secondary prevention of coronary heart disease

Abstract

Olpasiran and pelacarsen are gene-silencing therapies that lower lipoprotein(a). Cardiovascular outcome trials are ongoing. Mendelian randomisation studies estimated clinical benefits from lipoprotein(a) lowering. Our study estimated prices at which olpasiran and pelacarsen, in addition to standard-of-care, would be deemed cost-effective in reducing risk of recurrent coronary heart disease (CHD) events in the Australian healthcare system. We developed a decision tree and lifetime Markov model. For olpasiran, participants had CHD and lipoprotein(a) 260 nmol/L at baseline and three-monthly injections, profiled on OCEAN(a) Outcomes trial (NCT05581303). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a) from treatment. Mendelian randomisation study data were used to estimate downstream clinical benefits. Annual discounting was 5 %. For pelacarsen, participants had CHD and lipoprotein(a) 226 nmol/L at baseline and one- monthly injections, profiled on Lp(a) HORIZON (NCT04023552) trial. Olpasiran in addition to standard-of-care saved 0.87 discounted quality-adjusted life years (QALYs) per person. Olpasiran in addition to standard-of-care would be cost- effective at annual prices of AU$1867 (AU$467 per dose) at threshold AU$28,000 per QALY. Pelacarsen would be cost-effective at annual prices of AU$984 (AU$82 per dose). For ICER threshold AU$50,000 per QALY, olpasiran and pelacarsen would be cost-effective at annual prices AU$4207 and AU$2464 respectively. This early health technology assessment model used inclusion criteria from clinical trials. Olpasiran and pelacarsen would be cost-effective if annual treatment prices were AU$1867 and AU$984 respectively, from the Australian healthcare perspective.