US POPULATION ELIGIBILITY AND ESTIMATED PREVENTABLE CARDIOVASCULAR DISEASE EVENTS FROM INCLISIRAN TREATMENT

Therapeutic Area

Pharmacologic Therapy

Background

Many patients do not reach recommended low-density lipoproteincholesterol (LDL-C) levels on statin therapy alone. Inclisiran is a first-in-class siRNA therapy approved for lowering LDL-C, providing approximately 50% further LDL-C reduction. We estimated the number of US adults meeting inclisiran eligibility criteria and the number of potentially preventable atherosclerotic cardiovascular disease (ASCVD) events.

Methods

From the 2011-2020 National Health and Nutrition Examination Surveys (NHANES) we identified 3 potential patient cohorts: 1. high-risk primary prevention (>20% 10-year ASCVD risk or 7.5 - <20% plus two risk enhancing factors), 2. diabetes, and 3. secondary prevention with ASCVD aged >18 years with LDL-C>70 mg/dL (>55 mg/dL if very high risk ASCVD) despite statin therapy. NHANES sample weighting was used to project inclisiran eligibility for the US population. For estimated number of ASCVD events in 10 years “without inclisiran” the ASCVD Pooled Cohort Equation was applied to the high-risk primary prevention and diabetes cohorts and the SMART2 Risk Score was applied to the secondary prevention cohort. Relative risk reductions for ASCVD events were estimated by extrapolating the risk reductions observed in the Cholesterol Treatment Trialists (CCT) Collaboration with the achieved LDL-C metaanalysis reduction results from inclisiran Phase III trials. These risk reductions were then applied to our estimated eligible sample for inclisiran as identified above to estimate the preventable ASCVD events “with inclisiran”. Analysis for eligibility and preventable events was stratified by age, sex, and ethnicity.

Results

Among high-risk primary prevention, diabetes, and secondary prevention cohorts we estimated 9.05 million (M), 6.47M, and 7.98M US adults, respectively to be eligible for inclisiran. Based on 34.5% (primary prevention), 29% (diabetes) and 29% (secondary prevention) estimated respective risk reductions from inclisiran, we estimated 860,585, 459,809, and 710,990 ASCVD events could be preventable over 10 years of inclisiran treatment (Figure). Most preventable ASCVD events occurred among high-risk primary prevention, males and white persons.

Conclusions

We estimate over 23M US adults with inadequately controlled LDL-C despite statin therapy may be eligible for inclisiran treatment, with the potential to prevent 2.0M ASCVD events over 10 years. Earlier inclisiran initiation has the potential to significantly reduce adverse ASCVD outcomes.