Wholesale Acquisition Cost Research Articles

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment

The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Trends in Prices of Drugs Used to Treat Metastatic Non–Small Cell Lung Cancer in the US From 2015 to 2020

Oncology drug prices are a determinant of health disparities in the US and worldwide. Several new therapeutic agents for non-small cell lung cancer (NSCLC) have become available on the US market over the past decade. Although increased competition typically produces lower prices, competition among brand-name oncology drugs has not resulted in lower prices. To assess price changes in class-specific brand-name medications used to treat metastatic NSCLC in the US from 2015 to 2020. This cross-sectional study, conducted from August 13, 2015, to August 13, 2020, used data from the Micromedex Red Book and Medi-Span Price Rx databases. The study sample was limited to 17 brand-name medications used to treat metastatic NSCLC that were available for purchase before January 1, 2019. The main outcomes were trends over time in average wholesale prices and wholesale acquisition cost unit prices and the correlation in price among the multiple brand-name medications within each therapeutic class (immune checkpoint inhibitors, epidermal growth factor receptor inhibitors, anaplastic lymphoma kinase inhibitors, ROS1 inhibitors, BRAF inhibitors, and MEK inhibitors), measured using the Pearson correlation coefficient. The compounded annual growth rates of different medication costs were compared with the annual inflation rate and the consumer price index for prescription drugs. For all drug classes, the Pearson correlation coefficient approached 1.0, indicating an increase in drug list prices despite within-class drug competition. The median Pearson correlation coefficient values were 0.964 (range, 0.951-0.994) for immune checkpoint inhibitors, 0.898 (range, 0.665-0.950) for epidermal growth factor receptor inhibitors, 0.999 (range, 0.982-0.999) for anaplastic lymphoma kinase inhibitors, and 0.999 for BRAF and MEK inhibitors. The median compounded annual growth rates for most drug costs were higher than the annual inflation rate and consumer price index for prescription drugs: 1.81% (range, 1.29%-2.13%) for immune checkpoint inhibitors, 2.56% (range, 2.38%-5.26%) for epidermal growth factor receptor inhibitors, 2.46% (range, 1.75%-4.66%) for anaplastic lymphoma kinase and ROS1 inhibitors, and 3.06% (range, 0%-3.06%) for BRAF and MEK inhibitors. In this cross-sectional study, prices of brand-name medications for treatment of NSCLC increased in the US from 2015 to 2020 without evidence of price competition, raising concern about the affordability of promising oncology drugs. These findings suggest that drug pricing reform is needed.

Comparing Diagnosis and Treatment of Pulmonary Hypertension Patients at a Pulmonary Hypertension Center versus Community Centers.

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% (n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% (n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05–419,641.05, a monthly saving of USD 6964.70–7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition.

POSA145 Budget Impact of Zanubrutinib to Treat Relapsed or Refractory Marginal Zone Lymphoma from a Payer Perspective in the United States

Marginal zone lymphoma (MZL) is a heterogeneous, rare non-Hodgkin lymphoma that follows a prolonged remitting and relapsing course. The pivotal Phase 2 MAGNOLIA trial suggests that zanubrutinib had high response rates and durable disease control with a favorable safety profile in patients with relapsed/refractory (r/r) MZL. This study aimed to assess the budget impact of zanubrutinib treating adult patients with r/r MZL who had previously received ≥1 prior anti-CD20–based regimens. A 3-year Excel-based model was developed to estimate the budget impact of adding zanubrutinib to the formulary of a 1 million (M) member health plan from a US payer perspective. Comparators included ibrutinib, bendamustine-rituximab, rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone (RCHOP), rituximab-monotherapy, and lenalidomide. Dosing and treatment schedules were obtained from clinical trial publications. Costs of drug acquisition, administration, monitoring, and AE management costs (2020 US$) were obtained from RED BOOK, Centers for Medicare & Medicaid Services fee schedules, National Fee Analyzer, and Healthcare Cost and Utilization Project, respectively. Projected market shares were applied to estimate the number of patients treated with each regimen with and without zanubrutinib. Model outputs include annual budget impact and per member per month cost (PMPM) differences. Sensitivity analyses tested the impact of input uncertainty on modeled outcomes. In a hypothetical 1M members health plan, 11 patients (0.001%) were estimated to have at least 1 prior therapy and initiate treatment for r/r MZL. Adding zanubrutinib is associated with an average incremental budget impact of $45,018 ($0.004 PMPM), $67,527 ($0.006 PMPM), and $90,036 ($0.008 PMPM) in year 1, year 2, and year 3 respectively. Model results were most sensitive to zanubrutinib wholesale acquisition cost. Zanubrutinib offers an important treatment option for treating r/r MZL. Providing access to zanubrutinib for patients with r/r MZL is associated with minimal budget impact to a US health plan.

Financial Impact of an Automated Oncology Dose-Rounding Initiative: One-Year Analysis.

Infusion drugs are regarded as one of the high-cost health care expenditures. One approach to decrease drug expenditures is by dose-rounding biologics and cytotoxic agents. The Hematology/Oncology Pharmacy Association recommends that biologic and cytotoxic agents are rounded to the nearest vial size if they are within 10% of the ordered dose. The purpose of this initiative is to determine the impact of an automated dose-rounding algorithm on drug expenses. The dose-rounding algorithm was developed and integrated into the computerized physician order entry system for automated dose rounding to minimize impact on current workflow and to reduce medication errors. Twenty-four medications were preselected for dose rounding and included in the analysis. Ordered doses were automatically rounded to the nearest vial size if the dose was within 10% of the original dose. Prescribers then either reviewed and signed the rounded dose or manually entered the nonrounded dose. Cost savings were calculated as drug expense savings from doses rounded down. From July 2018 to June 2019, 10,206 doses of the selected medications were administered. Dose rounding occurred in 5,069 doses (49.7%). All 24 medications within the initiative were administered within the time of analysis. Of the rounded doses administered, 2,516 (49.6%) were rounded down to a commercially available vial size. Using wholesale acquisition cost pricing, the drug expense savings was approximately $3.6 million US dollars (USD). The medications with the highest savings were trastuzumab and ipilimumab, with annual savings of $756,780 USD and $494,517 USD, respectively. The automated dose-rounding algorithm at Michigan Medicine reduced drug expenditures substantially, and its integration within the computerized physician order entry system had minimal impact on current workflow.

Cost per Responder Analysis for Pegcetacoplan and Eculizumab in the Treatment of Adults with Paroxysmal Nocturnal Hemoglobinuria

Background: In the absence of clinical guidelines for paroxysmal nocturnal hemoglobinuria (PNH), the European Society for Blood and Marrow Transplantation (EBMT) developed categories for classifying hematological response to complement inhibitor treatment (per Risitano AM, et al. Front Immunol. 2019;10:1157). These categories are: complete (no transfusions, normal stable Hb, and no evidence of hemolysis); major (no transfusions, normal Hb, but evidence of residual intravascular/extravascular hemolysis); good (no transfusions, but persistent chronic mild anemia); partial (persistent chronic moderate anemia and/or occasional red blood cell transfusions); minor (3-6 transfusions every 6 months); no response (>6 transfusions every 6 months). In the phase 3 PEGASUS trial (NCT03500549), 41 and 39 patients previously treated with C5 inhibitors with Hb<10.5 were randomized for treatment with pegcetacoplan or eculizumab, respectively. In a post hoc analysis of the 16-week PEGASUS data, patients were classified by EBMT category to compare hematologic responses of each treatment (per Risitano AM, et al. Blood. 2020; 136(Suppl1):44-5).Objectives: The objective of this study was to evaluate the number needed to treat (NNT) and treatment costs of pegcetacoplan and eculizumab using EBMT response criteria.Methods: The analysis used a United States payer perspective and included drug acquisition costs and associated intravenous or subcutaneous administration costs. Drug costs were calculated using dosages for each treatment as given in the PEGASUS trial, including dosage and frequency escalations. Weekly dosages were multiplied by each drug's wholesale acquisition costs from RedBook (2020 United States dollars). We calculated the following outcomes over 16 weeks and by treatment: NNT to achieve each level of response, mean cost per treated patient, total costs, mean cost per treated patient per week, cost per complete responder, cost per good responder, and cost spent on patients with partial/minor/no response.Additional analyses were conducted to calculate outcomes for treatment-naïve patients treated with pegcetacoplan using similar post hoc analyses of combined 16-week data from the phase 1b-2a PADDOCK/PALOMINO (NCT02588833 and NCT03593200) trials.Results: Results are summarized in Table 1. Based on response rates, patients with PNH treated with pegcetacoplan had a lower NNT (1.4) to achieve good-to-complete response compared with eculizumab (19.5). NNT to achieve complete response was 2.6 for pegcetacoplan; no patients treated with eculizumab achieved complete response at 16 weeks.For the PEGASUS trial, mean cost per treated patient was $182,762 (with C5 inhibitor loading dose) and $176,504 over 16 weeks for pegcetacoplan and eculizumab, respectively. Among the 41 pegcetacoplan-treated patients, the total costs were $7,493,256 over 16 weeks. Of 41 pegcetacoplan patients, 16 achieved a complete response, and their total costs were $2.9 million over the 16-week period ($468,328 per complete responder). The total 16-week costs were $2.6 million for 14 patients with good response ($535,233 per good responder). For the 39 eculizumab-treated patients, total 16-week costs were $6,883,637. Two of 39 patients achieved a good response, and their total costs were $353,007 ($3,441,818 per good responder). Of the 39 patients, 37 achieved partial, minor, or no response or discontinued treatment, for a total cost of $6.5 million. This resulted in 95% of total treatment costs being spent on inadequate or no response in the eculizumab arm compared with 27% in the pegcetacoplan arm.For treatment-naïve patients treated with pegcetacoplan, the mean cost per complete responder ($347,339) and per good responder ($496,198) over 16 weeks were both lower than the cost per responder for patients treated with either pegcetacoplan or eculizumab after previous C5 inhibitor treatment.Conclusion: Based on the treatment response observed in PEGASUS, the NNT and cost to achieve good or good-to-complete response was lower for pegcetacoplan-treated patients than eculizumab-treated patients, according to EBMT consensus-based hematological response categories. PNH treatment with pegcetacoplan allowed more patients to achieve EBMT defined good-to-complete response and better overall response and is a more efficient use of spending with lower cost per responder in all response categories. [Display omitted] DisclosuresAnderson: Apellis: Consultancy, Research Funding. Talbird: Apellis: Consultancy, Research Funding. Fishman: Apellis: Current Employment, Current equity holder in publicly-traded company.

Comparative Cost-Efficiency Analysis of Trilaciclib, a Novel CDK4/6 Inhibitor, in the Prophylaxis of Chemotherapy-Induced Myelosuppression

Introduction. Trilaciclib (Cosela TM), a first-in-class breakthrough therapy, is a novel kinase CDK4/6 inhibitor that protects multiple hematopoietic lineages simultaneously by transiently arresting hematopoietic stem and progenitor cells (HSPC) in the G1 phase of the cell cycle and thus protecting HSPCs from damage by cytotoxic chemotherapy. Administered intravenously prior to the start of chemotherapy, it proactively delivers multilineage myeloprotection and therefore has the potential to improve the 3 major clinical manifestations of chemotherapy-induced myelosuppression (CIM): neutropenia, anemia, and thrombocytopenia. Trilaciclib was approved by the FDA in February 2021 and included in the NCCN Guidelines® in March 2021 for managing CIM in patients with extensive-stage small cell lung cancer (ES-SCLC) treated with a platinum/etoposide-containing or topotecan-containing regimen. As an alternative to single lineage-specific interventions with biological agents for neutropenia ([peg]filgrastim, ), anemia ([darb]epoetin alfa, alfa), and thrombocytopenia (romiplostim), trilaciclib may offer economic value in the prophylaxis and/or management of these adverse events. Cost-efficiency analysis evaluates the costs of various scenarios of delivering treatments to identify the most efficient cost-structure contributing to the value equation. The objective of this cost-efficiency analysis was to determine the savings (losses) in drug costs of managing 1 patient at risk for concurrent neutropenia and anemia and thrombocytopenia (NAT), neutropenia and anemia (NA), neutropenia and thrombocytopenia (NT), or anemia and thrombocytopenia (AT) with trilaciclib as opposed to any combination of biologicals, including biosimilars.Methods. Drug cost inputs included the wholesale acquisition cost (WAC; per REDBOOK; all agents) and the average sales price (ASP; per Centers for Medicare and Medicaid Services; all agents except trilaciclib as no ASP is available yet). An average cost was calculated for biosimilars. Dosing schedules were based on the maximum possible dose therapy in the NCCN Guidelines®. An Excel model was developed to calculate, for the 4 scenarios of CIM and the 32 WAC and ASP cost inputs across all agents, the drug cost for every possible combination of originator and biosimilar agents for 1 patient. These estimates were compared to the WAC of trilaciclib to determine the differential cost-efficiency of trilaciclib in terms of savings ($) accrued or losses (-$) incurred. This analysis focused on treatment with biological agents recommended in the NCCN Guidelines®. It did not consider platelet and red blood cell transfusion for thrombocytopenia and hence is limited to patients for whom transfusion is contra-indicated, physician decision to use romiplostim, or patient preference.Results. Table 1 presents the lowest, highest, mean, and median WAC and ASP differentials by chemotherapy-induced myelosuppression scenario. Mean and median differentials indicated cost savings with trilaciclib use across all chemotherapy-induced myelosuppression scenarios, with the exception of the ASP (with trilaciclib WAC) NA scenarios where losses were noted. Depending on single agents needed, savings ranged from $485.57 (AT ASP) to $9,531.60 (NAT WAC) per patient; with mean/median savings ranging from $646.36/$533.81 (AT ASP) to $7,397.69/$7,358.31 per patient.Conclusions. Myeloprotection with trilaciclib is a cost-efficient intervention when compared to managing individual or multiple myelosuppressive events with single-lineage, supportive care therapies. Unsurprisingly, costing conclusions are affected by the selection of an appropriate price benchmark. ASP tends to fluctuate more than WAC and is typically lower hence an ASP-based cost model may likely underrepresent the cost-efficiency of trilaciclib, as may be the case in the neutropenia/anemia scenario.(Data will be updated by conference time with the trilaciclib ASP if available). [Display omitted] DisclosuresMcBride: BMS: Current Employment. Henry: CVS Health: Current Employment. MacDonald: Matrix45, LLC: Current holder of individual stocks in a privately-held company. Abraham: Matrix45, LLC: Current holder of individual stocks in a privately-held company. OffLabel Disclosure:This presentation will discuss the use of romiplostim for the management of chemotherapy induced thrombocytopenia, an indication for which it has not received FDA approval.

The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations.

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection (RET) inhibitor indicated for the treatment of RET-positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET-mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET-positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.

North Dakota, which once lost its fight to regulate PBM practices, gets a rematch

North Dakota, which once lost its fight to regulate PBM practices, gets a rematch

Guided therapy selection in rheumatoid arthritis using a molecular signature response classifier: an assessment of budget impact and clinical utility.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose.

Medicare Part D spending for the 10 costliest oral anticancer drugs.

52 Background: Novel oral targeted drugs are being used more frequently to treat many cancers and have substantially improved clinical and survival outcomes. Due to the long treatment durations of many of these medications, which are given continuously until patient progression, per-patient lifetime costs can be high. This study aimed to identify the ten oral anticancer therapies with the highest annual Medicare Part D spending. Methods: Descriptive statistics were performed on data obtained from the CMS Medicare Part D Drug Spending Dashboard and IBM Micromedex RED BOOK, from 2018-2019. Medicare Part D dashboard includes total and average drug spending, and number of beneficiaries utilizing the drug. RED BOOK provides current and historical average wholesale pricing (AWP) data for all prescription drugs. The wholesale acquisition cost (WAC) was calculated from the AWP to evaluate trends in price. We identified the ten anticancer brand-name medications in 2019 with the highest annual Part D spending and reported changes in average spending and number of unique beneficiaries for each drug from 2018-2019. Results: In 2019, Revlimid had the highest annual total Part D spending at $4.6 billion, followed by Imbruvica with $2.4 billion; these drugs also had the greatest number of beneficiary utilizers. From 2018-2019, change in average spending per dosage unit was greatest for Zytiga (34%), however among all drugs, average spending per beneficiary in 2019 was lowest for this medication ($58,074). From 2018-2019, WAC and average spending per dosage unit increased for all of the top ten drugs, as well as the number of total beneficiaries utilizing each drug, except for Zytiga and Sprycel. Conclusions: Oral anticancer therapies provide high value for patients, including improved quality of life and survival. Annual costs for these drugs are high, however spending on inpatient hospital services remains a greater share of total Medicare spending in aggregate and on a per beneficiary basis. Emerging one-time curative treatments for cancer may prove most cost-effective in the long-term by eliminating the need for continuous medication use and hospital care, while improving patient outcomes.[Table: see text]

The cost-effectiveness of therapeutic drug monitoring for the prescription drug-based treatment of chronic myeloid leukemia.

BACKGROUND: A recent study demonstrating the use of Therapeutic Drug Monitoring (TDM) in patients with chronic myeloid leukemia (CML) resulted in a higher response rate with imatinib (IM) than demonstrated in second-generation tyrosine kinase inhibitor studies. The cost-effectiveness of TDM combined with IM (IM TDM) in first-line CML treatment has not yet been studied. OBJECTIVES: To determine the cost-effectiveness of IM TDM for the first-line treatment of CML compared to tyrosine kinase inhibitor only treatment. METHODS: A recently published cost-effectiveness model of tyrosine kinase inhibitor-treatment in CML was modified to include IM TDM as a first-line tyrosine kinase inhibitor-based CML treatment option. Efficacy inputs for major molecular response (MMR) rates were taken from previously published studies: IM TDM 65%, dasatinib 52%, nilotinib 53%. Annual tyrosine kinase inhibitor drug prices were derived from the Federal Supply Schedule (FSS) and the average and lowest wholesale acquisition costs (WAC) reported in the Red Book; the annual cost of TDM was $228. Other input costs modeled in the original CML CEA model were updated to 2016 US dollars using the medical service component of the Consumer Price Index. A US payer perspective was used with a 5-year time horizon and a 3.0% discount rate. The model compared first-line IM TDM versus IM alone, nilotinib (NIL) or dasatinib (DAS) in terms of the following outcomes: costs, quality-adjusted life-years (QALYs), and cost-effectiveness (total cost/QALY). Deterministic and probabilistic sensitivity analyses were performed using all key clinical and economic parameters. RESULTS: This study found that IM TDM dominates IM alone with $15,452 to $36,940 in savings and 0.25 higher QALYs. Using FSS, per patient total costs for IM and IM TDM were $270,905 and $233,965, respectively.; Using average WAC, these costs were $461,657 and $446,205, and using lowest WAC, these costs were $366,966 and $350,090. The results comparing first line using of IM TDM to NIL/DAS found that TDM IM had higher QALYs and lower costs (0.08 QALYs lower, and $117,006 to $172,420 savings per patient [varying by price basis]). Thus, in terms of cost-effectiveness, IM TDM dominates NIL/DAS with both lower costs and higher QALYs. CONCLUSIONS: IM TDM is a clinically and economically viable first-line treatment option for CML. DISCLOSURES: This study was funded by Saladax Biomedical. Salamone is an employee of Saladax Biomedical. This study was presented at the IATDMCT Congress, September 2018, Brisbane, Australia.

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States

To assess the cost-effectiveness and cost-effective price of tisagenlecleucel, a novel, effective chimeric antigen receptor T-cell therapy, versus salvage chemotherapy (SC) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) using a willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY) gained from a US third-party payer's perspective. A three-state (progression-free survival, progressive disease, and death), responder-based partitioned survival model with a lifetime horizon and 3% annual discount rate was developed. Overall survival (OS) and progression-free survival of tisagenlecleucel were estimated separately for patients with and without an overall response (OR), using data from JULIET ( Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients). OS of SC was informed by SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research). Mixture cure models were used to inform the survival of tisagenlecleucel responders, supported by JULIET. The median OS was 11.1 months in all tisagenlecleucel-treated patients but not reached for responders; no progression or death occurred among responders since month 22 of treatment. For tisagenlecleucel nonresponders and SC, survival was based on standard parametric models until month 60and the survival of DLBCL long-term survivors thereafter. The model prediction validated well against the observed trial data. Costs and utilities were from the literature; utilities depended on health states and were used to estimate QALYs. Total costs, QALYs, and incremental cost per QALY gained were estimated. A cost-effective price range was estimated for all tisagenlecleucel-treated patients, OR responders, and complete response (CR) responders. Deterministic sensitivity and scenario analyses and a probabilistic sensitivity analysis were performed. All costs were reported in or inflated to 2020 US dollars. Tisagenlecleucel was associated with 3.35 QALYs gained versus SC.,The estimated incremental costs per QALY gained versus SC were $78,652 using the wholesale acquisition cost of $373,000 for tisagenlecleucel. The estimated cost-effective price of tisagenlecleucel in all treated patients was $612,270 at the WTP threshold of $150,000. Tisagenlecleucel OR and CR responders had an increase of 7.82 and 9.34 QALYs versus SC, with cost-effective prices estimated at $1,281,456 and $1,551,974, respectively. Sensitivity analysis results supported the base case findings. Tisagenlecleucel is a cost-effective treatment versus SC for r/r DLBCL from the perspective of a US third-party payer. The estimated cost-effective prices ranged from $612,270 (all tisagenlecleucel-treated patients) to up to $1.5 million (patients achieving CR). Limitations include the use of single-arm trials due to data availability.

Cost-Consequence Analysis of Using Cangrelor in High Angiographic Risk Percutaneous Coronary Intervention Patients: A US Hospital Perspective.

ObjectivesThe objective of this study was to evaluate a US hospital’s cost implications and outcomes of cangrelor use in percutaneous coronary intervention (PCI) patients with two or more angiographic high-risk features (HRFs), including avoidance of oral P2Y12 inhibitor pretreatment in patients requiring cardiac surgery. Intravenous cangrelor provides direct, immediate onset and rapid-offset P2Y12 inhibition, which may reduce the necessity for oral P2Y12 pretreatment.MethodsA decision analytic model was developed, estimating the annual impact over 3 years of cangrelor availability. Ischemic and bleeding events (48 h) from randomized clinical trial data were extrapolated to 30 days. Event costs were from the CHAMPION PHOENIX Economics substudy. Rates of coronary artery disease (CAD) presentation, PCI, oral P2Y12 pretreatment, and inpatient hospitalization costs were from published literature and clinical experts. Scenario analyses evaluated the impact of cangrelor availability on potential reduced P2Y12 pretreatment rates by 50–100%. Drug costs were 2019 wholesale acquisition costs and, where necessary, all costs were adjusted to 2019 dollars.ResultsIn a hospital treating 1000 CAD PCI inpatients annually, increasing cangrelor use from 11 to 32% resulted in a reduction in 48-h ischemic events/year by 5.7%, while bleeding events increased by 2.9%. Total costs of $1,135,472 declined 12.8%, with a 50% reduction in P2Y12 pretreatment or 30% with no pretreatment. Savings were driven by a decrease in ischemic events, decrease in glycoprotein IIb/IIIa inhibitor use, and less need for and shorter oral P2Y12 inhibitor washout period for surgery patients.ConclusionUse of cangrelor in patients with two or more angiographic HRFs may improve outcomes and lower hospital budgets, mainly from avoiding surgery delays necessitated by oral P2Y12 inhibitor pretreatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-021-00491-9.

Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics

Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short-term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost-effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed.

Cost-Effectiveness of Daratumumab Plus Lenalidomide Plus Dexamethasone Versus Lenalidomide Plus Dexamethasone for Treatment of Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy: An Analysis of the Pollux Trial

Background: Daratumumab has been approved in the United States (US) for patients with multiple myeloma (MM). In the POLLUX trial of MM patients who had received at least one prior line of therapy, daratumumab plus lenalidomide plus dexamethasone (DRd) showed significant improvements in efficacy compared to lenalidomide plus dexamethasone (Rd) (Dimopoulos, NEJM, 2016). However, limited information is available on the cost-effectiveness of DRd. A decision-analytic model was developed to consider direct medical costs from a US payer perspective and to explore the cost-effectiveness of DRd versus Rd in previously treated MM and in a subgroup of patients with only one prior line of therapy (first relapse).Methods: The model structure took the form of a partitioned survival analysis with three health states: progression-free survival (PFS), progressive disease, and death. A range of parametric survival functions were fitted to patient-level PFS data from the POLLUX trial with (1) selection based on the Akaike and Bayesian information criteria and (2) priority given to the external validity of extrapolations with conservative survival projections. Diagnostic plots were used to assess the validity of the proportional hazards assumption between DRd and Rd. Due to the number of data events and the follow-up time of the trial, overall survival (OS) was not estimated via parametric extrapolation of trial data but rather by its relationship to PFS, based on a retrospective analysis of approximately 23,000 MM patients (Felix, BMC Cancer, 2013). Drug costs were taken from wholesale acquisition costs (Red Book, 2017). Dosing information was extracted from the POLLUX trial. Drug-administration costs were sourced from Centers for Medicare and Medicaid Services, 2017 and health-state costs, subsequent therapy utilization patterns, and utility weights were sourced from published literature. Cost-effectiveness was estimated over a lifetime horizon, with costs and outcomes discounted at 3% per annum. Incremental cost-effectiveness ratios were calculated, specifically the incremental cost per quality-adjusted life-year (QALY) gained and the incremental cost per life-year gained. One-way and probabilistic sensitivity analyses (PSA) were conducted, as well as scenario analyses around parametric curve selection. All analyses were performed for the overall trial population and for the subgroup of patients with a first relapse.Results: The best-fit, conservative parametric function for all patients was Weibull and for first relapse patients, exponential. All results were presented as discounted values (Table 1). In the overall trial population, the mean PFS was estimated to be 4.12 and 1.84 years for DRd and Rd, respectively. DRd resulted in an average of 4.24 additional life-years (8.43 life-years - 4.19 life-years) and 3.66 additional QALYs (7.12 QALYs - 3.46 QALYs) over Rd. Costs increased for DRd; the majority were related to drug acquisition of daratumumab and to longer time on treatment due to a longer PFS period. Incremental cost-effectiveness ratios in the overall trial population were $153,110 per life-year gained and $177,499 per QALY gained. Overall, survival (life-years), PFS, and QALYs were greater in the first relapse subgroup for both DRd and Rd than in the overall trial population. Mean PFS was estimated to be 5.02 and 2.09 years for DRd and Rd, respectively. DRd resulted in an average of 4.83 additional life-years (9.51 life-years - 4.68 life-years) and 4.17 additional QALYs (8.06 QALYs - 3.89 QALYs) over Rd. Incremental cost-effectiveness ratios in the first relapse subgroup were $165,167 per life-year gained and $191,024 per QALY gained. One-way and scenario analyses indicated the most sensitive parameters to be PFS distribution, the relationship between PFS and OS, discount rates, utility weights, and drug-acquisition costs. PSA was summarized in the form of scatter plots and cost-effectiveness acceptability curves.Conclusion: Based on the range of plausible cost-effectiveness ratio thresholds ($183,000-$264,000 per life-year gained and $109,000-$297,000 per QALY gained) reported in the 2003 cost-effectiveness decision rules for the US (Braithwaite, Med Care, 2008), this analysis suggests that DRd is cost-effective compared to Rd in the treatment of previously treated MM. DRd offers a clinically superior and cost-responsible treatment option for previously treated MM. [Display omitted] DisclosuresMaiese:Janssen: Employment; Johnson & Johnson, LLC: Equity Ownership. Graham:Janssen: Research Funding; RTI Health Solutions: Employment. Hawe:RTI Health Solutions: Employment; Janssen: Research Funding. Le Moine:RTI Health Solutions: Employment; Janssen: Research Funding. Abraham:Janssen Oncology (Johnson & Johnson, LLC): Consultancy. Senbetta:Johnson & Johnson, LLC: Equity Ownership; Janssen: Employment.

Cost-Effectiveness of Daratumumab Plus Bortezomib and Dexamethasone Versus Bortezomib Plus Dexamethasone for Treatment of Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy: An Analysis of the Castor Trial

Background: Daratumumab has recently been approved in the United States (US) for patients with multiple myeloma (MM). In the CASTOR clinical trial of patients who had received at least one prior line of therapy, daratumumab plus bortezomib and dexamethasone (DVd) showed significant improvements in clinical efficacy compared to bortezomib plus dexamethasone (Vd) (Palumbo, NEJM, 2016). However, limited information is available on the cost-effectiveness of DVd. A decision-analytic model was developed to consider direct medical costs from a US payer perspective and to explore the cost-effectiveness of DVd versus Vd in previously treated MM and in a subgroup of patients with only one prior line of therapy (first relapse).Methods: The model structure took the form of a partitioned survival analysis with three health states: progression-free survival (PFS), progressive disease, and death. A range of parametric survival functions were fitted to patient-level PFS data from the CASTOR trial with (1) selection based on the Akaike and Bayesian information criteria and (2) priority given to the external validity of extrapolations with conservative survival projections. Diagnostic plots were used to assess the validity of the proportional hazards assumption between DVd and Vd. Due to the number of data events and the follow-up time of the trial, overall survival (OS) was not estimated via parametric extrapolation of trial data but rather by its relationship to PFS, based on a retrospective analysis of approximately 23,000 MM patients (Felix, BMC Cancer, 2013). Drug costs were taken from wholesale acquisition costs (Red Book, 2017). Dosing information was extracted from the CASTOR trial. Drug-administration costs were sourced from Centers for Medicare and Medicaid Services, 2017 and health-state costs, subsequent therapy utilization patterns, and utility weights were sourced from published literature. Cost-effectiveness was estimated over a lifetime horizon, with costs and outcomes discounted 3% per annum. Incremental cost-effectiveness ratios were calculated, specifically the incremental cost per quality-adjusted life-year (QALY) gained and the incremental cost per life-year gained. One-way and probabilistic sensitivity analyses were conducted, as well as scenario analyses around parametric curve selection. All analyses were performed for the overall trial population and for the subgroup of patients with a first relapse.Results: The best-fit, conservative parametric function for all patients was the generalized gamma and for first relapse patients, Weibull. All results were presented as discounted values (Table 1). In the overall trial population, the mean PFS was estimated to be 1.50 and 0.67 years for DVd and Vd, respectively. DVd resulted in an average of 1.92 additional life-years (3.50 life-years - 1.58 life-years) and 1.62 more QALYs (2.88 QALYs - 1.26 QALYs) over Vd. Costs increased for DVd; the majority were related to drug acquisition of daratumumab and to longer time on treatment due to a longer PFS period. Incremental cost-effectiveness ratios in the overall population were $94,446 per life-year gained and $112,338 per QALY gained. Overall, survival (life-years), PFS, and QALYs were greater in the first relapse subgroup for both DVd and Vd than in the overall trial population. Mean PFS was estimated to be 2.56 and 0.80 years for DVd and Vd, respectively. DVd resulted in an average of 3.84 more life-years (5.74 life-years - 1.90 life-years) and 3.23 more QALYs (4.78 QALYs - 1.55 QALYs) over Vd. Incremental cost-effectiveness ratios in the first relapse subgroup were $68,628 per life-year gained and $81,681 per QALY. One-way and scenario analyses indicated the most sensitive parameters to be PFS distribution, the relationship between PFS and OS, discount rates, utility weights, and drug-acquisition costs. PSA was summarized in the form of scatter plots and cost-effectiveness acceptability curves.Conclusion: Based on the range of plausible cost-effectiveness ratio thresholds ($183,000-$264,000 per life-year gained and $109,000-$297,000 per QALY gained) reported in the 2003 cost-effectiveness decision rules for the US (Braithwaite et al., Med Care, 2008), this analysis suggests that DVd is cost-effective compared to Vd in the treatment of previously treated MM. DVd offers a clinically superior and cost-responsible treatment option for previously treated MM. [Display omitted] DisclosuresMaiese:Johnson & Johnson, LLC: Equity Ownership; Janssen: Employment. Graham:RTI Health Solutions: Employment; Janssen: Research Funding. Hawe:RTI Health Solutions: Employment; Janssen: Research Funding. Le Moine:Janssen: Research Funding; RTI Health Solutions: Employment. Abraham:Janssen Oncology (Johnson & Johnson, LLC): Consultancy. Senbetta:Janssen: Employment; Johnson & Johnson, LLC: Equity Ownership.

Budget Impact Analysis of CPX-351 in the Treatment of Patients with Treatment-Related Acute Myeloid Leukemia (tAML) or AML with Myelodysplasia-Related Changes (MRC) from a US Payer Perspective

AML is a rapidly progressing and life-threatening blood cancer that disproportionately affects older adults. The treatment paradigm in AML has seen little change in the past 4 decades, with intensive chemotherapy with a 7-day continuous infusion of cytarabine plus an anthracycline such as daunorubicin on Days 1-3 (ie, “7+3” regimen) remaining the standard-of-care induction therapy for AML. CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio into leukemia cells. In a phase 3 study (NCT01696084), CPX-351 demonstrated superior overall survival (9.56 vs 5.95 months; HR = 0.69; P= 0.005) and significantly improved complete remission rate (38% vs 26%; P= 0.040) compared with 7+3 in the treatment of elderly patients with newly diagnosed tAML or AML-MRC (Lancet JE, et al. ASCO 2016. Abstr 7000). Additionally, CPX-351 is administered as a 90-minute infusion on Days 1, 3, and 5 (induction cycle 1 only), and offers the potential for outpatient administration. The aim of this study was to estimate the budget impact associated with the introduction of CPX-351 for the treatment of patients with tAML or AML-MRC from a US payer perspective.A decision analytic model was developed to estimate the budget impact of using CPX-351 compared with 7+3 for induction and consolidation treatment of AML patients with tAML and AML-MRC. The decision algorithm was developed based on clinical practice guidelines from the National Comprehensive Cancer Network and validated by an oncologist. Epidemiology estimates were from SEER 2017. Clinical outcomes (response rate and incidence of adverse events [AE]) and site of care were from the CPX-351 phase 3 pivotal trial. In that study, CPX-351 was administered in the outpatient setting for 51% of patients in consolidation cycle 1 and 61% in cycle 2, compared with 6% and 0% of 7+3 patients in consolidation cycles 1 and 2 (Kolitz JE, et al. ASCO 2017. Abstr 7036). Administration costs were from CMS for Medicare and InGauge Healthcare Solutions for commercial costs. Hospital costs were from the CMS Limited Data Set. H-CUP National Inpatient Sample was used to estimate the AE costs by payer type. Drug costs were wholesale acquisition costs. The model did not include costs for hematopoietic cell transplant.For a hypothetical 1 million-member plan, it is estimated that there are approximately 12 patients with tAML and AML-MRC each year. Increasing the use of CPX-351 from year 1 to 3 (assumption of year 1 = 20%, year 2 = 50%, and year 3 = 80%) resulted in cost increases compared with 7+3 (year 1 = $7,471 to year 3 = $29,884, or <$0.01 per member per month increase in each year). Over the same time period, the estimated number of responders increased from 3.06 with 7+3 to 4.19 with CPX-351. The increased level of responses with CPX-351 reduced the cost/responder from $358,695 with 7+3 to $269,106 by year 3 following introduction of CPX-351. Of note, outcomes are derived from a phase 3 randomized, controlled trial of CPX-351 versus 7+3, the model did not account for potential regimen changes, and costs may not be generalizable across all settingsThis model predicted that the use of CPX-351 may be associated with improved patient outcomes and limited budget impact from the payer perspective. DisclosuresJensen:Celator/Jazz: Consultancy. Wu:Celator/Jazz: Consultancy. Sacks:Celator/Jazz: Consultancy. Cyr:Celator/Jazz: Consultancy. Chung:Baxter: Equity Ownership; Shire: Equity Ownership; Baxalta: Equity Ownership; Amgen: Equity Ownership; Gilead: Equity Ownership; Bayer: Equity Ownership; Gilead: Employment; Jazz Pharmaceuticals: Employment, Equity Ownership.

Is Obinutuzumab Plus Chemotherapy Followed By Obinutuzumab Monotherapy for Previously Untreated Follicular Lymphoma Patients Cost-Effective in the US?

BackgroundObinutuzumab (GA101; G) in combination with chemotherapy followed by G maintenance (G+chemo) has demonstrated superior progression-free survival (PFS) relative to the combination of Rituximab and chemotherapy followed by R maintenance (R+chemo) for previously untreated patients with follicular lymphoma (FL) in the phase III GALLIUM clinical trial (NCT01332968) (Hiddemann et al., European Hematology Association, 2017). The net clinical benefit and economic value of G+chemo vs. R+chemo in a previously untreated FL patient population have not been formally evaluated. The objective of this study was to estimate the cost-effectiveness of G+chemo vs. R+chemo based on results of the GALLIUM trial.MethodsIn the GALLIUM trial, patients received chemotherapy (8 x 21-day cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], 8 x 21-day cycles of cyclophosphamide, vincristine, and prednisone [CVP], or 6 x 28-day cycles of bendamustine) and were randomized to receive either R 375mg/m2 on Day (D) 1 of each cycle or G 1000mg on D1, 8 and 15 of Cycle 1 and D1 of subsequent cycles. Patients with a complete response or partial response at the end of induction as per modified Cheson criteria received R or G every 2 months for 2 years or until disease progression. We developed a Markov model that utilized the GALLIUM trial's independent review committee (IRC) assessed progression-free survival (PFS), and post-progression survival (PPS) to model overall survival (OS). Drug utilization, treatment duration and adverse events were based on trial data. Costs include drugs, adverse events, monitoring and follow-up care upon disease progression; health care costs were based on Medicare reimbursements and drug costs were July 2017 average sale price (ASP) for intravenous therapies or wholesale acquisition cost (WAC) for oral therapies used post-progression. Utility estimates were based on the GALLIUM trial data and published literature to derive the quality of life impact and compute the quality-adjusted life years (QALY). Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results.ResultsTreatment with G+chemo led to an increase in quality-adjusted life years (QALYs) relative to R+chemo of 0.79 (95% Credible Range (CR) 0.19, 1.36) (Table 1). The total cost of G+chemo was $217,000 and R+chemo was $215,100 resulting in an incremental cost of $1,800 (95% CR: -$7,800, $10,000). The average total cost was greater for G+chemo due primarily to increased drug and administration costs ($137,100 for G+chemo vs. $126,300 for R+chemo), however this was largely offset by cost-savings for disease progression of -$10,100 ($75,700 for G+chemo vs. $85,600 for R+chemo). Adverse event costs were higher for G+chemo ($4,200) vs. R+chemo ($3,300). The incremental cost-effectiveness ratio was $2,249 per QALY gained. In probabilistic sensitivity analyses, there was a 98% and 99% probability that G+chemo was cost-effective versus R+chemo at the $50,000 and $100,000 per QALY thresholds, respectively. There was a high probability G+chemo was cost effective even when all parameters in the model were varied.ConclusionsOur US-based analysis suggests that treatment with G+chemo compared to R+chemo is cost-effective in previously untreated patients with FL. The cost-effectiveness of G+chemo is driven by delaying expensive progression treatments and increasing quality adjusted life years. In conclusion, G+chemo vs. R+chemo in previously untreated FL patients is very likely cost effective in the US. [Display omitted] DisclosuresGuzauskas:Genentech, Inc.: Consultancy. Masaquel:Genentech Inc.: Employment, Other: I Receive Roche stock options. Thuresson:F. Hoffmann-La Roche Ltd: Employment. Li:Genentech: Employment, Equity Ownership. Reyes:Genentech Inc.: Employment, Equity Ownership. Veenstra:Genentech, Inc.: Consultancy.

Economic Evaluation for the US of Venetoclax Versus Allogeneic Hematopoietic Stem-Cell Transplantation for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia with 17p Deletion

Background: Until the advent of targeted agents, the primary treatment for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) with 17p deletion (del(17p)) was allogeneic hematopoietic stem cell transplantation (HSCT). Venetoclax is a targeted therapy that has been shown to effect significant progression free (PFS) and overall survival (OS) with an acceptable safety profile and the convenience of oral administration. HSCT is potentially curative but is associated with potential transplant-associated morbidity and mortality (incl. graft-versus-host disease) and relapse. Both treatments are expensive, HSCT largely up-front and venetoclax long term, with relative differences in cost of treatment and supportive care management. Considering these different efficacy, safety, and procedural profiles, we evaluated the cost-effectiveness and cost-utility of venetoclax versus HSCT in R/R CLL del(17p) from a US payer perspective.Methods: A life time horizon Markov model was constructed specifying 3 health states: PFS with embedded sub-states specifying whether patient is on or off therapy, progression, and death. Data sources to simulate the R/R CLL del(17p) patients included Stilgenbauer et al (Lancet Oncol 2016) for venetoclax and Schetelig et al (J Clin Oncol 2008) for HSCT. Kaplan-Meier PFS and OS curves were digitized, PFS and OS data extracted, and Weibull distributions fitted to these data for both venetoclax and HSCT. The wholesale acquisition cost of venetoclax was sourced from RedBook. Costs of the HSCT procedure, pre-conditioning treatment, and post-procedural side effects were estimated from published prediction equations and national private claims database. EQ-5D utility values were sourced from published literature. Disutility values for side effects were assumed same for both interventions. A discount rate of 3% was applied when survival exceeded one year. Following extrapolation to a life time horizon, the life years (LY) and quality adjusted LY (QALY) for each treatment were estimated, and the incremental LY and QALY gained with venetoclax over HSCT calculated. From the respective total treatment costs, cost differentials and the incremental cost effectiveness (ICER) and cost utility ratios (ICUR) were determined. Base case analyses were validated by probabilistic sensitivity analyses (PSA) of 2000 iterations.Results: Venetoclax prevailed in PFS over HSCT until ~190 weeks (3.7 years) when curves crossed and HSCT prevailed. Venetoclax prevailed in OS over HSCT over the full life time horizon. As shown in the Table, in the life time Markov model, compared to HSCT, venetoclax showed cost savings of -$360,995 (PSA: -$350,350) and incremental gains of 0.64 (PSA: 0.62) LY and 0.39 (PSA: 0.37) QALY. This yielded an ICER of savings of -$564,054 (PSA: -$565,080) per LY gained and an ICUR of savings of -$925,628 (PSA: -$946,891) per QALY gained.Conclusion: Against a life time horizon, venetoclax prevails in OS and for ~3.7 years in PFS over HSCT in the management of patients with R/R CLL del(17p). Yielding a cost saving by ~$565,000 if LYs gained are concerned but by ~$945,000 in the case of QALYs gained, it has the life time benefit of being clinically superior in combined OS and safety at markedly lower cost. While surviving HSCT-treated patients had improved outcomes with a slightly higher likelihood of subsequent PFS than venetoclax-treated patients, this marginal benefit is dominated by the significantly higher probability of OS for patients with venetoclax therapy. Venetoclax provides significantly greater life time clinicoeconomic value in the treatment of patients with R/R CLL del(17p) versus HSCT. [Display omitted] DisclosuresPersky:Genentech: Consultancy; MorphoSys: Other: Independent Data Monitoring Committee member ; Verastem: Consultancy; Spectrum Pharmaceuticals: Research Funding. Abraham:Janssen Oncology (Johnson & Johnson, LLC): Consultancy.