The price at which inclisiran is cost effective adjunctive to standard of care (SoC) versus SoC alone in US adults with atherosclerotic cardiovascular disease and elevated low-density lipoprotein cholesterol ≥70 mg/dL, despite maximum tolerated doses of statins (with or without ezetimibe), was investigated at willingness-to-pay thresholds of $50,000, $100,000 and $150,000 per quality-adjusted life-year (QALY). |
Inclisiran was found to be cost effective at the evaluated thresholds, at a price ranging from $6383 to $13,563 per year ($3191 to $6782 per dose). |
At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. |
1 Introduction
2 Methods
2.1 Population
Parameters | Base-case value | Distribution | Source | |
---|---|---|---|---|
Baseline characteristics | ||||
Age (mean) | 66.04 | NA | ORION-10 patient-level data | |
Female | 31% | NA | ||
Diabetes | 45% | NA | ||
Baseline LDL-C, mg/dL (weighted average) | 104.97 | NA | ||
Distribution of treatments across SoC subcategories | ||||
Taking ezetimibe | Not taking statins | 1.9% | NA | |
Low-intensity statins | 0.1% | NA | ||
Moderate-intensity statins | 1.4% | NA | ||
High-intensity statins | 6.1% | NA | ||
Not taking ezetimibe | Not taking statins | 8.9% | NA | |
Low-intensity statins | 0.6% | NA | ||
Moderate-intensity statins | 17.3% | NA | ||
High-intensity statins | 63.7% | NA | ||
Baseline LDL-C across SoC subcategories, mg/dL | ||||
Taking ezetimibe | Not taking statins | 151.90 | NA | |
Low-intensity statins | 90.00 | NA | ||
Moderate-intensity statins | 104.81 | NA | ||
High-intensity statins | 106.37 | NA | ||
Not taking ezetimibe | Not taking statins | 151.80 | NA | |
Low-intensity statins | 131.90 | NA | ||
Moderate-intensity statins | 104.53 | NA | ||
High-intensity statins | 96.75 | NA | ||
Distribution across subpopulations from event rate dataa | ||||
ACS 0–1 | 1.9% | NA | Optum Clinformatics® Data Mart analysis (data on file) | |
ACS 1–2 | 1.8% | NA | ||
ACS stable | 1.8% | NA | ||
IS 0–1 | 2.7% | NA | ||
IS 1–2 | 2.6% | NA | ||
IS stable | 2.6% | NA | ||
PAD 0–1 | 9.4% | NA | ||
PAD 1–2 | 9.5% | NA | ||
PAD stable | 9.7% | NA | ||
Other CHD 0–1 | 19.4% | NA | ||
Other CHD 1–2 | 19.3% | NA | ||
Other CHD stable | 19.3% | NA | ||
Rate ratios applied per 1 mmol reduction in LDL-C (adjusting real-world probabilities for SoC) | ||||
Revascularization | 0.75 | Log normal (95% CI 0.72–0.78) | Armitage et al. [39] | |
NF-MI | 0.73 | Log normal (95% CI 0.70–0.76) | ||
Vascular death | 0.84 | Log normal (95% CI 0.80–0.88) | ||
IS | 0.79 | Log normal (95% CI 0.74–0.85) | ||
Rate ratios applied per 1 mmol reduction in LDL-C (adjusting SoC probabilities for inclisiran—year 1) | ||||
Revascularization | 0.89 | NA | Based on adjustment from Collins et al., 2016 [25] | |
NF-MI | 0.89 | NA | ||
Vascular death | 0.92 | NA | ||
IS | 0.91 | NA | ||
Rate ratios applied per 1 mmol reduction in LDL-C (adjusting SoC probabilities for inclisiran—after year 1) | ||||
Revascularization | 0.71 | NA | Based on adjustment from Collins et al., 2016 [25] | |
NF-MI | 0.69 | NA | ||
Vascular death | 0.80 | NA | ||
IS | 0.75 | NA | ||
Annual probabilities of CV mortalityb | ||||
MI | 14.50% | Beta (95% CI 0.12–0.17) | Krumholz et al. [46] | |
UA | 6.44% | Beta (95% CI 0.05–0.07) | Krumholz et al. [46] | |
Stroke | 12.20% | Beta (95% CI 0.10–0.14) | Krumholz et al. [46] | |
Revascularization | 2.66% | Beta (95% CI 0.02–0.03) | Peterson et al. [47] | |
PAD | 1.78% | Beta (95% CI 0.015–0.021) | Law et al. [48] | |
Other CHD | 1.78% | Beta (95% CI 0.015–0.021) | Assumed same as PAD | |
Other adjustments | ||||
Annual increase in NF events | 3% | NA | TA393 [19] | |
Annual increase in fatal events | 5% | NA | ||
Proportion of deaths that are CV-related | 62% | NA | CTT collaboration, 2012 [45] | |
SMR: CV mortality >1 year vs. before 1 year after event—CHD (men) | 0.63 | Log normal (95% CI 0.54–0.73) | Smolina et al. [49] | |
SMR: CV mortality >1 year vs. before 1 year after event—CHD (women) | 0.69 | Log normal (95% CI 0.58–0.79) | Smolina et al. [49] | |
SMR: CV mortality >1 year vs. before 1 year after event—stroke | 0.29 | Log normal (95% CI 0.20–0.39) | Dennis et al. [50] | |
SMR: second event of the same kind vs. after first event | 1.5 | Log normal (95% CI 1.28–1.73) | Smolina et al. [49] | |
Treatment efficacy | ||||
Inclisiran LDL-C reduction | 52.3% | Beta (95% CI 0.50–0.53) | Ray et al. [18] | |
Annual discontinuation rate—statins | 23% | Beta (95% CI 0.20–0.26) | Burke et al. [26] | |
Annual discontinuation rate—inclisiran | 11.5% | Beta (95% CI 0.06–0.21) | Freemantle et al. [27] | |
Discontinuation cap—statins | 20% | NA | Unpublished data | |
Discontinuation cap—inclisiran | 20% | NA | Unpublished data | |
Costs—drug costs and resource use | ||||
Simvastatin—average of 10 mg and 20 mg—cost per pack | $2.36 | NA | Micromedex Red Book [37] | |
Atorvastatin 40 mg—cost per pack | $7.28 | NA | ||
Ezetimibe—cost per pack | $8.50 | NA | ||
Total SoC—cost per year | $77.40 | NA | Calculated | |
Injection procedure cost | $14.31 | Gamma (95% CI 12.16–16.46) | Centers for Medicare and Medicaid Services [51] | |
Outpatient visit cost | $92.47 | (95% CI 78.60–106.34) | ||
Costs—health state costs | ||||
MI—acute | $66,476 | Gamma (95% CI 56,504–76,447) | Fox et al. [29] | |
UA—acute | $44,853 | Gamma (95% CI 38,123–51,581) | ||
Stroke—acute | $47,037 | Gamma (95% CI 39,981–54,092) | ||
Revascularization—acute | $62,032 | Gamma (95% CI 52,727–71,337) | ||
CV death—acute | $22,065 | Gamma (95% CI 18,755–25,374) | Bhatt et al. [30] | |
MI—year 1 | $13,628 | Gamma (95% CI 11,584–15,672) | Fox et al. [29] | |
UA—year 1 | $9142 | Gamma (95% CI 7771–10,513) | ||
Stroke—year 1 | $9892 | Gamma (95% CI 8408–11,375) | ||
MI—year 2, MI—stable | $14,468 | Gamma (95% CI 12,298–16,638) | ||
UA—year 2, UA—stable | $9651 | Gamma (95% CI 8204–11,099) | ||
Stroke—year 2, Stroke—stable | $14,440 | Gamma (95% CI 12,274–16,605) | ||
Revascularization—stable | $7703 | Gamma (95% CI 6548–8859) | ||
General population utility regression | ||||
Coefficient—baseline | 0.893 | Beta (95% CI 0.89–0.90) | Bhatt et al. [30] | |
Coefficient—age-adjustment factor | − 0.001 | Normal (95% CI – 0.001 to –0.000) | ||
Coefficient—mean age in the study by Bhatt et al. | 59 | NA | ||
Utilities—secondary prevention population utility multipliersc | ||||
MI | 0.965 | Beta (95% CI 0.95–0.98) | ||
UA | 0.906 | Beta (95% CI 0.87–0.94) | ||
Stroke | 0.884 | Beta (95% CI 0.84–0.91) | ||
Revascularization | 0.986 | Beta (95% CI 0.98–0.99) | Kazi et al. [32] | |
PAD | 0.965 | Beta (95% CI 0.95–0.98) | Assumed same as MI | |
Other CHD | 0.965 | Beta (95% CI 0.95–0.98) | Assumed same as PAD | |
Disutilities for CV events | ||||
UA—year 1 | − 0.021 | Normal (95% CI – 0.05 to 0.00) | Bhatt et al. [30] | |
MI—year 1 | − 0.028 | Normal (95% CI – 0.03 to – 0.02) | ||
Stroke—year 1 | − 0.073 | Normal (95% CI – 0.09 to – 0.06) | ||
UA—year 2 | − 0.001 | Normal (95% CI – 0.02 to – 0.01) | ||
MI—year 2 | − 0.023 | Normal (95% CI –0.03 to – 0.02) | ||
Stroke—year 2 | − 0.069 | Normal (95% CI – 0.08 to – 0.06) | ||
UA—year 2+ | − 0.001 | Normal (95% CI – 0.02 to 0.01) | ||
MI—year 2+ | − 0.023 | Normal (95% CI – 0.03 to – 0.02) | ||
Stroke—year 2+ | − 0.069 | Normal (95% CI – 0.08 to – 0.06) | ||
Revascularization—year 2+ | 0.002 | Normal (95% CI 0.00–0.01) | ||
Disutility for injection | ||||
Disutility for injection | − 0.0015 | Normal (95% CI – 0.0013 to – 0.0017) | Matza et al. [35] |
2.2 Model Structure
2.3 Baseline Risk of Cardiovascular Events
2.4 Treatment Strategies
2.5 Costs and Utilities
2.6 Outcomes
2.7 Sensitivity Analyses
Input | Detail | Base-case value used | Scenario value used | ||||||
---|---|---|---|---|---|---|---|---|---|
Discontinuation | Assuming the minimum proportion remaining on inclisiran or statins was 40% | 20% | 40% | ||||||
Assuming no discontinuation for any treatments (inclisiran, statins, ezetimibe) | 11.5% inclisiran 23% statins/ezetimibe | 0% | |||||||
Health state costs | Alternative costs for MI and stroke states | Acute | Year 1 | Year 2/stable | Acute | Year 1 | Year 2/stable | ||
MI | $66,845 | $13,704 | $14,548 | MI | $22,675 | $39,890 | $6096 | ||
Stroke | $47,298 | $9947 | $14,520 | Stroke | $22,675 | $39,890 | $6096 | ||
Efficacy of inclisiran | Using alternative efficacy for inclisiran from a NMA | 52.3% | 56.06% [52] | ||||||
Cost of inclisiran | Using the published list price of inclisiran | NA | $3250 per dose |
3 Results
3.1 Base-Case Analysis
Technologies | Inclisiran cost-effective price per dose | Inclisiran cost-effective price per year | Total costs ($) | Total LYG | Total QALYs | Incremental costs ($) | Incremental LYG | Incremental QALYs |
---|---|---|---|---|---|---|---|---|
$50,000 WTP threshold | ||||||||
SoC | – | $121,184 | 11.27 | 9.41 | – | – | – | |
Inclisiran + SoC | $3191 | $6383 | $142,682 | 11.76 | 9.84 | $21,498 | 0.50 | 0.43 |
$100,000 WTP threshold | ||||||||
SoC | – | $121,184 | 11.27 | 9.41 | – | – | – | |
Inclisiran + SoC | $4987 | $9973 | $164,174 | 11.76 | 9.84 | $42,990 | 0.50 | 0.43 |
$150,000 WTP threshold | ||||||||
SoC | – | $121,184 | 11.27 | 9.41 | – | – | – | |
Inclisiran + SoC | $6782 | $13,563 | $185,666 | 11.76 | 9.84 | $64,482 | 0.50 | 0.43 |