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Supplementary Material
Figure S1. Disease Progression Model Structure
Adult HOFH.png

Note: A patient in any health state can transition to either CV death or non-CV death at any time.

Table S1. Model Assumptions

  • CV event reduction was causally linked to changes in LDL-C levels.

  • Evolocumab was assumed to be a representative PCSK9 inhibitor in the model but was not included based on its lack of use in the source that informed SOC treatment distribution.

  • Atorvastatin was used as a representative statin in the model.

  • Transitions from the TIA or SA health states to the UA, MI, or stroke health states were permitted, but reverse transitions were not allowed.

  • Urgent revascularization was assumed to occur following a CV event (e.g., MI or UA), and its associated costs were assumed to be captured within the cost estimates of those respective health states. The model does not include elective revascularization.

  • The treatment effect on LDL-C reduction observed at 24 weeks was assumed to persist for the entire time horizon of the model, or until treatment discontinuation.

  • Patients in any of the post-event health states could not move back to the SA or TIA health states. This is because allowing transitions to less severe states could result in implausible improvements in costs and health utility. To maintain logical consistency, transitions were restricted to reflect only disease progression.

  • Costs associated with the treatment of adverse events were not included in the model, consistent with precedent and based on data-driven considerations.

  • The model allowed for treatment discontinuation of lomitapide up to week 24. LDL-C lowering and consequently any CV risk benefits were assumed to stop immediately upon treatment discontinuation.

  • There was no treatment discontinuation for SOC over the model time horizon, consistent with a prior NICE technology appraisal in HoFH.¹²

  • The health-state cost for stable HoFH was assumed to be zero, consistent with precedent and based on external expert feedback.

  • The frequency of apheresis for each treatment was assumed to be stable over time.

  • The reduction in apheresis due to treatment with lomitapide began at week 104 based on the end of the safety phase of the APH-19 trial.

Abbreviations: CV, cardiovascular; HoFH, homozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PCSK9, proprotein convertase subtilisin/kexin type 9; SA, stable angina; SOC, standard of care; TIA, transient ischemic attack; UA, unstable angina.

Abbreviations: SOC, standard of care.

Table S2. Treatment Utilization and Discontinuation Inputs

ᵃThe distributions from Ward et al. (2007)23 for patients aged 45–54 years were used in the model for patients aged 40–54 years and <40 years, consistent with the method used in a prior NICE technology appraisal in HoFH.¹²

ᵇA relative risk of 1.5 was applied for subsequent cardiac (SA, UA, and MI) or cerebrovascular (TIA and stroke) events after an initial cardiac or cerebrovascular event, respectively, and for CV death after any prior CV event²⁵ A relative risk of 1.2 was applied for cardiac events after an initial cerebrovascular event and vice versa.

Abbreviations: CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; SA, stable angina; TIA, transient ischemic attack; UA, unstable angina.

Table S3. Inputs for Initial CV Events and Relationship Between LDL-C and CV Risk

Note: Costs inputs are rounded to the closest whole dollar for presentation herein but were not rounded in the model.

ᵃFor lomitapide + SOC, the blood sample appointment frequency is based on the assumption that blood samples will be collected at every GP and specialist appointment.

Abbreviations: GP, general practitioner; HbA1c, hemoglobin A1c; SOC, standard of care.

Table S4. Monitoring and Procedure Resource Use and Cost Inputs
References

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