Stakeholder perspectives on the sustainability of the United States biosimilars market.

Biologic therapies play a critical role in modern medical practice but also present challenges for payers, patients, and other stakeholders because of their high cost. Biosimilars can mitigate the cost pressures of reference biologic therapy because they are typically priced at least 25% lower, providing a means to administer cutting-edge biologic therapy while also managing cost of care. In fact, the US health care system has saved an estimated $23.6 billion from use of biosimilars. However, the market is still in a nascent phase of development, and early cost-saving successes are not guaranteed to persist unless sustainable market conditions are established. To better understand the perspectives of stakeholders about opportunities and threats to the sustainability of the US biosimilar market, a multistakeholder roundtable discussion was convened in December of 2023 and included health care payers, providers, self-insured employers, a manufacturer, and a biosimilar research and advocacy organization. The objective of this commentary, authored by the roundtable participants, is to posit specific opportunities and threats that stakeholders should consider to better facilitate sustainable biosimilar market conditions in the United States. We highlight key points, including (1) biosimilar price volatility with large quarter-on-quarter declines for most products; (2) perverse economic incentives that encourage providers to use more expensive reference products because reimbursement dynamics make them more profitable; (3) complex rebate structures that create barriers to biosimilar access; and (4) ongoing changes to the legal and regulatory environment, including evidence requirements to gain "interchangeable" status. We conclude with an overview of potential policy solutions to address the sustainability opportunities and threats. The authors welcome the opportunity to advance this dialogue toward action and encourage additional stakeholders to join the effort. We are optimistic that, through informed decision-making and compromise, we can collectively achieve a robust and sustainable US biosimilars market that appropriately benefits all stakeholders.

A descriptive analysis of real-world oncology biosimilar use in Japan.

Aim: To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. Methods: This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated. Results: Overall, 14-39% of biosimilar-prescribed patients initiated therapy with reference products. Biosimilar utilization significantly increased from 2019 to 2022. The most-commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy. Conclusion: Reference products were most frequently prescribed among the Japanese cohorts, but substantial and increasing proportions received biosimilars over time. Future studies should extend our initial insights to assess biosimilar clinical outcomes in Japanese settings.

This study examines the adoption of cancer biosimilar therapies in Japan from 2019 to 2022. Cancer biosimilars are complex treatments that closely resemble established cancer therapies already available in Japan. We looked into the characteristics of patients receiving three specific biosimilars ­ bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer. We also investigated where patients received biosimilar treatment, other therapies they received alongside biosimilars and the proportion of patients using these therapies each year during the study. Our analysis utilized data from the 'Medical Data Vision' database, which records care provided in hospitals across Japan. We analyzed patient demographics and treatment patterns, and compared different groups using statistics to identify significant differences. Notably, we observed that between 14 and 39% of patients initially started treatment with the original version of the drug on the market, known as the 'reference product,' before switching to the biosimilar. Furthermore, our findings revealed a significant increase in the use of biosimilars each year during the study period. Biosimilars were most-commonly used alongside chemotherapy drugs. These initial findings shed light on the patient population using cancer biosimilars in Japan and the treatment contexts in which they are utilized. Future research should delve deeper into aspects such as cost of care, patient survival, side effects and other pertinent factors related to the use of biosimilars in cancer care in Japan.

Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review.

Purpose: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer's biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio. Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation. Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value. Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.

Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.

Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102.

PURPOSE: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101.

BMT CTN 1101 was a Phase III randomized controlled trial comparing reduced-intensity conditioning followed by double unrelated umbilical cord blood transplantation (UCBT) versus HLA-haploidentical related donor bone marrow transplantation (haplo-BMT) for patients with high-risk hematologic malignancies. Here we report the results of a parallel cost-effectiveness analysis of these 2 hematopoietic stem cell transplantation (HCT) techniques. In this study, 368 patients were randomized to unrelated UCBT (n = 186) or haplo-BMT (n = 182). We estimated healthcare utilization and costs using propensity score-matched haplo-BMT recipients from the OptumLabs Data Warehouse for trial participants age <65 years and Medicare claims for participants age ≥65 years. Weibull models were used to estimate 20-year survival. EQ-5D surveys by trial participants were used to estimate quality-adjusted life-years (QALYs). At a 5-year follow-up, survival was 42% for haplo-BMT recipients versus 36% for UCBT recipients (P = .06). Over a 20-year time horizon, haplo-BMT is expected to be more effective (+.63 QALY) and more costly (+$118,953) for persons age <65 years. For those age ≥65 years, haplo-BMT is expected to be more effective and less costly. In one-way uncertainty analyses, for persons age <65, the cost per QALY result was most sensitive to life-years and health state utilities, whereas for those age ≥65, life- years were more influential than costs and health state utilities. Compared to UCBT, haplo-BMT was moderately more cost-effective for patients age <65 years and less costly and more effective for persons age ≥65 years. Haplo-BMT is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BMT is a preferred choice when considering costs and outcomes.

Translating an Economic Analysis into a Tool for Public Health Resource Allocation in Cancer Survivorship.

Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience. Highlights: Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.

Assessment of the Cost-Effectiveness of HER2-Targeted Treatment Pathways in the Neoadjuvant Treatment of High-Risk HER2-Positive Early-Stage Breast Cancer.

INTRODUCTION: This study aims to assess differences in costs and benefits of treatment strategies for high-risk human epidermal growth factor receptor 2 positive (HER2+) early-stage breast cancer (ESBC). METHODS: We used a hybrid decision-tree/Markov model to simulate costs and outcomes across six health states: Invasive disease-free, non-metastatic recurrence, remission, first-line and second-line metastatic cancer, and death. We considered several strategies, defined by four attributes: (1) Neoadjuvant targeted therapy (infused pertuzumab and trastuzumab (PH) versus subcutaneous fixed-dose combination (FDC) of pertuzumab and trastuzumab versus trastuzumab alone (H)); (2) adjuvant targeted therapy if pathological complete response (pCR) is achieved (PH, FDC, or H); (3) adjuvant targeted therapy (T-DM1 or H) in the case of residual disease (RD); and (4) use of branded or biosimilar H. Transition probabilities were derived from relevant clinical trials. We included drug costs and costs associated with adverse events and administration. Health state utilities were obtained from clinical trials and the literature. RESULTS: Strategies not containing T-DM1 were dominated (worse outcomes and greater costs) by strategies containing T-DM1. Among strategies with pertuzumab continuation in the case of pCR and T-DM1 in the case of RD, use of FDC was dominant (equivalent outcomes and lower costs), relative to strategies using infused therapies, regardless of biosimilar versus branded trastuzumab. Adjuvant continuation of FDC was also cost-effective (better outcomes at reasonable cost increases) relative to strategies which discontinued pertuzumab following pCR. CONCLUSION: Dual targeted therapy via FDC (with transition to T-DM1 in the case of RD) is a cost-effective treatment strategy in high-risk HER2+ ESBC.

Assessing Barriers to use of the Specific Carbohydrate Diet in Pediatric Inflammatory Bowel Disease: A Qualitative Study.

Because of the high cost and associated toxicities of pharmacotherapy treatment for inflammatory bowel disease (IBD), there has been growing interest in dietary therapy. The objective of this study is to assess barriers to initiating or maintaining the specific carbohydrate diet (SCD) to inform strategies for improving access and adherence to the diet. Methods: We conducted semistructured interviews with parents of 10 children with IBD receiving care at a single academic treatment center. Parents were eligible if their child with IBD was either currently on the SCD, previously on the SCD, or opted not to initiate the SCD. Core questions were developed in conjunction with IBD clinical experts. Interviews were transcribed and analyzed using an inductive approach. Results: Parents of children diagnosed with IBD primarily chose to try the SCD because of concerns about medication safety. Three major barriers to utilizing the SCD emerged: cost, time commitment, and psychosocial impact. Many parents also expressed that following the SCD got easier over time and some parents experienced spillover effects of improved personal health and understanding of nutrition. All parents were strong proponents of the importance of diet in managing IBD and expressed desire for more research into the SCD and other forms of dietary therapy. Conclusions: These findings provide important insight into factors affecting utilization of the SCD in pediatric IBD. Further research is needed to develop interventions or strategies to diminish these barriers and enable more patients to benefit from the SCD.

Potential Cost-Effectiveness of Risk-Based Pancreatic Cancer Screening in Patients With New-Onset Diabetes.

BACKGROUND: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. METHODS: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. RESULTS: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. CONCLUSIONS: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Patient Knowledge and Expectations About Return of Genomic Results in a Biomarker-Driven Master Protocol Trial (SWOG S1400GEN).

PURPOSE: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP). METHODS: Eligible participants with previously treated advanced non-small-cell lung cancer were recruited from patients enrolled in Lung-MAP. Participants completed a 38-item telephone survey ≤ 30 days from Lung-MAP consent. The survey assessed understanding about the benefits and risks of Lung-MAP participation and knowledge of the potential uses of somatic testing results returned. Descriptive statistics and odds ratios for associations between demographic factors and correct responses to survey items were assessed. RESULTS: From August 1, 2017, to June 30, 2019, we recruited 207 participants with a median age of 67, 57.3% male, and 94.2% White. Most participants "strongly/somewhat agreed" with statements that they "received enough information to understand" Lung-MAP benefits (82.6%) and risks (69.5%). In items asking about potential uses of Lung-MAP genomic results, 87.0% correctly indicated that the results help to select cancer treatment, but < 20% correctly indicated that the results are not used to confirm cancer diagnosis, would not reveal risk of developing diseases besides cancer, and would not indicate if family members had increased cancer risk. There were no associations between sociodemographic factors and proportions providing correct responses. CONCLUSION: In a large National Clinical Trials Network biomarker-driven master protocol, most participants demonstrated incorrect knowledge and expectations about the uses of genomic results provided in the study despite most indicating that they had enough information to understand benefits and risks.

A Budget Impact Analysis of Gene Therapy for Sickle Cell Disease: The Medicaid Perspective.

Importance: Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population. Objectives: To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model. Design, Setting, and Participants: A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease. Exposures: The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year. Main Outcomes and Measures: The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care. Results: An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact. Conclusions and Relevance: This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.

A comparison of mixture cure fraction models to traditional parametric survival models in estimation of the cost-effectiveness of nivolumab for relapsed small cell lung cancer.

BACKGROUND: In August 2018, the US FDA granted accelerated approval for nivolumab in small cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy and at least one other line of therapy. The objective of this study was to evaluate the cost-effectiveness of nivolumab vs. usual care as third-line (3 L) therapy for patients with recurrent SCLC (rSCLC) from the health payer perspective. Given the potential for a meaningful fraction of treated patients to achieve long-term response to nivolumab, we also assessed the impact of using mixture cure modeling (MCM) vs. parametric survival modeling on survival estimates and cost-effectiveness from the US Medicare payer perspective. METHODS: We created a partitioned survival decision model to assess the cost-effectiveness of 3 L nivolumab vs. usual care in rSCLC, based on observed US treatment patterns. Using this approach, we assessed the impact of extrapolating long-term survival from the CheckMate 032 trial, using both MCM and standard parametric curve fits. Nivolumab survival, resource use, and Grade 3/4 adverse event rates were derived from CheckMate 032. Usual care survival, resource use, and costs were derived from an analysis of patients receiving 3 L treatment for rSCLC in the SEER-Medicare registry. We applied 2020 Wholesale Acquisition Cost for drugs and 2020 CMS reimbursement for procedures. Utilities were derived from the literature. We estimated life years (LY), quality-adjusted life years (QALYs), and costs over a lifetime horizon. RESULTS: MCM and parametric survival model extrapolations resulted in 0.43 versus 0.38 more LYs, 0.34 versus 0.30 more QALYs, and $69,308 versus $61,336 more expenditure for nivolumab vs. usual care, respectively. The costs per QALY gained using mixture cure versus parametric survival modeling were $204,386 and $207,431, respectively. CONCLUSIONS: Mixture cure modeling was equivalent compared to parametric modeling in estimating the cost-effectiveness of nivolumab-based therapy due to the small fraction of patients achieving a long-term response with nivolumab (12.9%).

THE AUTHORS RESPOND.

DISCLOSURES: Funding for the study referred to in this letter was contributed by Bayer Healthcare. Xia and Williamson are employees of Bayer Healthcare. Roth, Carlson, and Sullivan are consultants to Bayer Healthcare. Carlson also reports fees from Adaptive Biotechnologies, unrelated to the study. Roth reports consulting fees from BMS, unrelated to the study.

Value and affordability of CAR T-cell therapy in the United States.

In the United States the increasing number of Food and Drug Administration (FDA)-approved, innovative, and potentially effective commercial cancer therapies pose a significant financial burden on public and private payers. Chimeric antigen receptor (CAR) T cells are prototypical of this challenge. In 2017 and 2018, tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Kite) were approved by the FDA for use after showing groundbreaking results in relapsed/refractory B-cell malignancies. In 2020 and 2021, four further submissions to the FDA are expected for CAR T-cell therapies for indolent and aggressive B-cell malignancies and plasma cell myeloma. Yet, with marketed prices of over $350,000 per infusion for the two FDA-approved therapies and similar price tags expected for the coming products, serious concerns are raised over value and affordability. In this review we summarize recent, peer-reviewed cost-effectiveness studies of tisagenlecleucel and axicabtagene ciloleucel in the United States; discuss key issues concerning the health plan budget impact of CAR T-cell therapy; and review policy, payment and scientific approaches that may improve the value and affordability of CAR T-cell therapy.

The Potential Long-Term Comparative Effectiveness of Larotrectinib and Entrectinib for Second-Line Treatment of TRK Fusion-Positive Metastatic Lung Cancer.

BACKGROUND: Larotrectinib and entrectinib are FDA-approved therapies for patients with non-small cell lung cancer (NSCLC) with neurotrophic receptor tyrosine kinase gene fusion (TRK fusion-positive) whose cancer has metastasized and progressed. Early evidence indicates that these targeted therapies may offer dramatic survival benefits versus traditional cytotoxic regimens, but it remains uncertain how larotrectinib and entrectinib compare with each other. OBJECTIVE: To simulate and compare expected life-years and quality-adjusted life-years (QALYs) for both TRK inhibitors. METHODS: We developed a partitioned survival model to project the long-term comparative effectiveness of larotrectinib versus entrectinib in second-line treatment of metastatic NSCLC. Larotrectinib survival data were derived from a 13-month follow-up of 12 patients with TRK fusion-positive NSCLC in the NCT02122913 (phase 1) and NCT02576431 (NAVIGATE) trials. Entrectinib survival data were derived from a 13-month follow-up of 10 patients with TRK fusion-positive NSCLC in the ALKA-372-001, STARTRK-1, and STARTRK-2 trials. For larotrectinib and entrectinib progression-free survival and overall survival (OS), in-trial survival was extrapolated using parametric curve fits. Exponential fits were selected for all survival models based on minimal Bayesian information criteria and clinical plausibility. Lifetime survival curves were used to estimate expected mean/median survival. QALYs were estimated by applying preprogression and postprogression health state utilities derived from the literature. RESULTS: In the base case, treatment with larotrectinib and entrectinib resulted in 5.4 and 1.2 median preprogression life-years and 7.0 and 1.8 median total life-years, respectively. Mean preprogression life-years (QALYs) were 7.5 (5.0) and 1.9 (1.2), and mean total life-years (QALYs) were 9.2 (5.8) and 4.4 (2.4), respectively. CONCLUSIONS: Among TRK inhibitors for metastatic NSCLC, larotrectinib is estimated to provide improved life-year and QALY outcomes versus entrectinib based on parametric extrapolations of in-trial survival data. Our analysis is limited by lack of NSCLC-specific data on entrectinib OS, the small samples of patients with NSCLC in the trials, and a cross-trial comparison. Future studies should re-evaluate the comparative effectiveness of larotrectinib versus entrectinib as more patients are treated and as long-term survival data mature. DISCLOSURES: Funding for this study was contributed by Bayer Healthcare, which reviewed the manuscript drafts, and employees contributed to the manuscript as coauthors. Xia and Williamson are employees of Bayer Healthcare. Roth, Carlson, and Sullivan are consultants to Bayer Healthcare and retain rights to all final revisions to the manuscript. Carlson also reports fees from Adaptive Biotechnologies, unrelated to this work. Roth reports consulting fees from BMS, unrelated to this work.

The Women's Health Initiative Estrogen-alone Trial had differential disease and medical expenditure consequences across age groups.

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials. METHODS: Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures. RESULTS: Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively. CONCLUSION: The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

Safety and Costs of Endobronchial Ultrasound-Guided Nodal Aspiration and Mediastinoscopy.

BACKGROUND: There remains debate over the best invasive diagnostic modality for mediastinal nodal evaluation. Prior studies have limited generalizability and insufficient power to detect differences in rare adverse events. We compared the risks and costs of endobronchial ultrasound (EBUS)-guided nodal aspiration and mediastinoscopy performed for any indication in a large national cohort. METHODS: We conducted a retrospective study (2007-2015) with MarketScan, a claims database of individuals with employer-provided insurance in the United States. Patients who underwent multimodality mediastinal evaluation (n = 1,396) or same-day pulmonary resection (n = 2,130) were excluded. Regression models were used to evaluate associations between diagnostic modalities and risks and costs while adjusting for patient characteristics, year, concomitant bronchoscopic procedures, and lung cancer diagnosis. RESULTS: Among 30,570 patients, 49% underwent EBUS. Severe adverse events-pneumothorax, hemothorax, airway/vascular injuries, or death-were rare and invariant between EBUS and mediastinoscopy (0.3% vs 0.4%; P = .189). The rate of vocal cord paralysis was lower for EBUS (1.4% vs 2.2%; P < .001). EBUS was associated with a lower adjusted risk of severe adverse events (OR, 0.42; 95% CI, 0.32-0.55) and vocal cord paralysis (OR, 0.57; 95% CI, 0.54-0.60). The mean cost of EBUS was $2,211 less than mediastinoscopy ($6,816 vs $9,023; P < .001). After adjustment this difference decreased to $1,650 (95% CI, $1,525-$1,776). CONCLUSIONS: When performed as isolated procedures, EBUS is associated with lower risks and costs compared with mediastinoscopy. Future studies comparing the effectiveness of EBUS vs mediastinoscopy in the community at large will help determine which procedure is superior or if trade-offs exist.