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Rationale & Objective Benefits of sodium-glucose co-transporter 2 inhibitors on kidney outcomes have been demonstrated in clinical trials. Among patients with type 2 diabetes and established cardiovascular (CV) disease enrolled in EMPA-REG Outcome Study (NCT01131676), empagliflozin added to standard of care (SoC) reduced the risk of incident or worsening nephropathy compared to SoC alone. This analysis evaluated the cost-effectiveness of empagliflozin versus SoC alone in the subpopulation with diabetic kidney disease (DKD) from the perspective of United States (US) commercial insurers and Medicare. Study Design Discrete event simulation model. Setting & Population Patients with DKD in a US healthcare system. Interventions Empagliflozin 10 or 25 mg with SoC versus SoC alone. SoC included glucose-lowering therapies and medications to treat CV risk factors. Outcomes Incremental cost-effectiveness ratios (ICERs, 2020 US dollars per quality-adjusted life-year [QALY] gained). Costs and QALYs were discounted 3.0%/year. Model, Perspective, & Timeframe: Cost-effectiveness analysis, commercial insurers and Medicare perspective, lifetime horizon. Results The ICER of empagliflozin with SoC versus SoC alone was $25,974/QALY. Empagliflozin added 0.67 QALYs and $17,322/patient over a lifetime horizon. Results were driven by fewer clinical events (including CV death, heart failure [HF] hospitalization, albuminuria progression, and a composite kidney outcome) experienced by patients receiving empagliflozin with SoC versus SoC alone. Results were sensitive to rates of CV death, non-fatal MI, and HF hospitalization, as well as to drug costs, and time horizon. Probabilistic sensitivity analyses indicated 91% of simulations falling below $50,000/QALY. Limitations The EMPA-REG Outcome Study was not powered to assess treatment benefits in a subgroup and excluded patients with estimated glomerular filtration rate Conclusion Based on EMPA-REG Outcome Study, this cost-effectiveness analysis suggests that for commercial insurers and Medicare, adding empagliflozin to SoC may be a cost-effective treatment option for patients with DKD.

Aim To estimate the cost‐effectiveness of sequential addition of empagliflozin versus sitagliptin after metformin in patients with type 2 diabetes (T2D) with or without cardiovascular disease (CVD) from the perspective of the US healthcare payer. Methods An individual simulation model predicted lifetime diabetes‐related complications, using UKPDS‐OM2 equations in patients without CVD, and EMPA‐REG OUTCOME equations in patients with CVD. Additional US‐based sources informed inputs for population characteristics, adverse events, non‐CV death, treatment escalation, quality of life and costs. Costs and quality‐adjusted life‐years (QALYs) were discounted 3.0% annually. Results The incremental cost‐effectiveness ratio (ICER) for second‐line empagliflozin versus sitagliptin in the overall T2D population was $6967/QALY. Empagliflozin led to longer CVD‐free survival (0.07 years) and an 11% reduction in CV death in patients with CVD compared with sitagliptin. Empagliflozin resulted in greater benefits with greater costs in patients with versus without baseline CVD, yielding ICERs of $3589/QALY versus $12 577/QALY, respectively. Results were consistent across a range of deterministic and probabilistic sensitivity analyses and scenarios. Conclusion Compared with sitagliptin, empagliflozin was cost‐effective (at $50 000/QALY US threshold) as a second‐line treatment to metformin for T2D patients with or without CVD in the United States. Our findings lend additional support for more widespread adoption of guidelines by healthcare decision‐makers for T2D treatment.

Background: Standard of care (SoC) for transfusion-dependent β-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective: This study investigates the cost-effectiveness of betibeglogene autotemcel (‘beti-cel’; LentiGlobin for β-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design: Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in turn determine risk of iron overload complications that increase mortality. Clinical trial data informed beti-cel clinical parameters; effects of SoC on iron levels came from real-world studies; iron overload complication rates and mortality were based on published literature. Setting: USA; commercial payer perspective Participants: TDT patients age 2–50 Interventions: Beti-cel is compared to SoC. Main outcome measure: Incremental cost-effectiveness ratio (ICER) utilizing quality-adjusted life-years (QALYs) Results: The model predicts beti-cel adds 3.8 discounted life years (LYs) or 6.9 QALYs versus SoC. Discounted lifetime costs were $2.28 M for beti-cel ($572,107 if excluding beti-cel cost) and $2.04 M for SoC, with a resulting ICER of $34,833 per QALY gained. Conclusion: Beti-cel is cost-effective for TDT patients compared to SoC. This is due to longer survival and cost offset of lifelong SoC.

Aims Heart failure (HF) and type 2 diabetes (T2D), common co‐morbidities, translate into worse patient prognoses and higher direct costs than for either condition alone. Empagliflozin has been shown to markedly reduce cardiovascular (CV) deaths and HF hospitalizations (HHF) in HF patients with T2D. This study evaluated the lifetime cost‐effectiveness of supplementing standard of care (SoC) with empagliflozin, relative to SoC alone, in HF patients with T2D from the UK payer perspective. Methods and results An existing discrete‐event simulation model was adapted for the economic evaluation. Risk equations developed from time‐dependent parametric survival analyses using patient‐level HF subpopulation data from the EMPA‐REG OUTCOME trial were employed to predict CV and renal events. Non‐CV death, utility weights, and costs were drawn from UK sources. Quality‐adjusted life years (QALYs) and costs were discounted at 3.5% per annum. Relative to SoC, empagliflozin with SoC yielded fewer first HHF, recurrent HHF, CV death, and non‐fatal myocardial infarction but more non‐fatal stroke events. Empagliflozin with SoC vs. SoC alone was associated with increased average life expectancy (10.80 vs. 9.59 LYs) and quality of life (6.27 vs. 5.62 QALYs), though at higher lifetime cost (£18 197 vs. £16 829) per person, resulting in an incremental cost‐effectiveness ratio of £2093 per QALY. The probability of empagliflozin being cost‐effective in the HF subpopulation at a £20 000 per QALY willingness‐to‐pay threshold was 91%. Conclusions This analysis suggests that adding empagliflozin to SoC in HF patients with T2D constitutes a cost‐effective use of UK healthcare resources and may provide long‐term health benefits to patients.

Background: The ADA’s “Standards of Medical Care in Diabetes” recommends use of an SGLT2 inhibitor or GLP-1 receptor agonist as one of the six drug classes after metformin (MET) in T2D patients. These therapies are preferred among T2D patients with cardiovascular disease (CVD) based on clinical trial results demonstrating significant improvement in clinical outcomes. We sought to examine the economic implications of sequential use of these therapies. Methods: An economic simulation model evaluating treatment in U.S. T2D patients after MET with empagliflozin (EMPA) as 2nd line and liraglutide (LIRA) as 3rd line vs. LIRA as 2nd line and EMPA as 3rd line was used to estimate the lifetime health and cost outcomes of T2D-related complications and adverse events (AEs). Complications, including CV death, myocardial infarction, stroke, and renal outcomes, were predicted using United Kingdom Prospective Diabetes Study risk equations and EMPA-REG OUTCOME data. A meta-analysis informed treatment-induced changes in HbA1c, SBP, and weight in patients without CVD. For each complication in patients with CVD, an indirectly estimated hazard ratio of LIRA vs. EMPA was applied. Costs ($2019), AE rates, and utilities were sourced from published literature. Results: Compared with LIRA as 2nd line, use of EMPA added 0.32 quality-adjusted life-years (QALYs) and led to lower lifetime costs (by $11,422/patient), suggesting dominance over 2nd line LIRA (improved health outcomes at lower cost). These results were similar across CVD subgroups. Patients with CVD at baseline compared to those without CVD showed larger gains in incremental QALYs (0.42 with CVD, 0.29 without CVD) with somewhat lower cost savings (by $9,550, $12,392, respectively) for 2nd line EMPA vs. LIRA, showing dominance in both subpopulations. Conclusion: For T2D patients with and without CVD, the use of EMPA on background MET was a dominant strategy for U.S. payers, associated with improved outcomes and lower costs as compared with LIRA. Disclosure O. Reifsnider: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Employee; Spouse/Partner; CVS Caremark. M.J.D. Stargardter: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. S. Brand: Consultant; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharmaceuticals, Inc. N. Desai: None. S. Shetty: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

IntroductionEmpagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease.Research design and methodsIndividual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients’ lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities.ResultsThe model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (−US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively.ConclusionsEmpagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs.

INTRODUCTION: The EMPA-REG OUTCOME trial demonstrated the efficacy of empagliflozin in the treatment of type 2 diabetes (T2D) with a previous history of cardiovascular (CV) disease. The drug is currently reimbursed for T2D Italian patients, but the reduction of CV mortality and morbidity shown in the trial opens a new treatment perspective in those patients with associated high CV risk.OBJECTIVE: Cost-effectiveness analysis of empagliflozin for the treatment of T2D patients with a previous history of CV disease, from the Italian National Health Service (NHS) perspective.METHODS: The analysis was performed with an individual simulation model, which can predict the time to CV events or death through a set of time-dependent regressions estimated on the patient-level data of the EMPA-REG OUTCOME trial. This design allows the direct simulation of long-term outcomes and costs without the need for surrogate endpoints.The model was adapted to the Italian setting, considering local epidemiological data, baseline quality of life (QoL) utility, background mortality and unit costs from current prices and tariffs. The cost perspective was that of the Italian NHS and the horizon of the simulation was lifetime. Costs and benefits were discounted at a 3.5% rate.RESULTS: Base case results were estimated on a cohort of 5,000 patients, which ensured the convergence of the simulation. Patients treated with empagliflozin in add-on to the standard of care (SoC) lived on the average 13.8 undiscounted years as compared to 11.8 years of patients on SoC alone. The gain in discounted quality-adjusted life years (QALYs) was 1.0, due to improved survival and QoL linked to the reduced incidence of CV events and CV mortality. The incremental cost-effectiveness ratio (ICER) was 4,811 €/QALY, well below the commonly applied threshold of 30,000-50,000 €/QALY.CONCLUSION: Empagliflozin in add-on to the SoC is a highly cost-effective strategy for the treatment of T2D patients with known CV disease in the Italian setting.

Objectives Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer. Methods A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM. Results The DES model's predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64–0.85 and final actual: 0.74; 95% CI 0.6–0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data. Conclusions Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes.

Background: A central goal of treatment for high-risk AML is enabling patients to receive HCT. CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. A large randomized, open-label, multicenter, phase 3 trial demonstrated superior outcomes, including significantly longer overall survival and a larger fraction of patients reaching HCT, for CPX-351 versus conventional cytarabine/daunorubicin (7+3 regimen) in patients aged 60 to 75 years with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC; Lancet JE, et al. J Clin Oncol. 2018). In order to estimate the cost-effectiveness of treatments for AML, and for CPX-351 in particular, it is necessary to extrapolate survival of patients undergoing HCT to the long-term. The objective of this analysis was to assess the impact of different estimates of post-HCT mortality on cost-effectiveness of CPX-351. Methods: An existing economic model of CPX-351 versus 7+3 for the treatment of tAML or AML-MRC was used to project lifetime health and cost outcomes. The modeled population included 30% patients Results: In the base case with different SMR values by age, the model yielded a predicted ICER value of $111,841/QALY in the overall cohort, which compares favorably to the typical $150,000/QALY threshold (Bae 2014) for good value care in the United States. Using the same estimates of SMR in all patients yielded ICER values of $125,280/QALY and $151,793/QALY for SMR values of 2.25 and 4.0, respectively. Assuming no excess mortality post-HCT relative to the general population, using an SMR of 1.0, resulted in modest improvements in cost-effectiveness (ICER = $102,298/QALY). Conclusions: CPX-351 is a cost-effective option for the treatment of patients with tAML or AML-MRC when accounting for potentially increased mortality following HCT. Disclosures Kansal: Jazz Pharmaceuticals: Consultancy. Reifsnider:Jazz Pharmaceuticals: Consultancy. Todorova:Jazz Pharmaceuticals: Employment, Equity Ownership. Coughlan:Jazz Pharmaceuticals: Consultancy. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership, Other: Stock and stock options.