Evolving Evidence-Based Value Assessment of One-Time Therapies: Tisagenlecleucel as a Case Study.

BACKGROUND: Economic evaluation of one-time therapies during reimbursement decision-making is challenging due to uncertain long-term outcomes. The availability of 5-year outcome data from the ELIANA trial and real-world evidence of tisagenlecleucel, the first chimeric antigen receptor T-cell (CAR-T) therapy, presents an opportunity to re-evaluate the predictions of prior cost-effectiveness analyses (CEAs). OBJECTIVE: To conduct a systematic literature review (SLR) of prior CEAs of tisagenlecleucel for pediatric/young adult relapsed or refractory acute lymphoblastic leukemia (r/r ALL) and evaluate the impact of recently available 5-year efficacy data from ELIANA and advances in CAR-T manufacturing in an updated CEA model. METHODS: OVID MEDLINE/Embase and health technology assessment (HTA) databases were searched for full-text economic evaluations in English reporting cost-effectiveness results for tisagenlecleucel for r/r ALL. Evaluations with publicly reported incremental cost-effectiveness ratios (ICERs) were included in the SLR. Study screening and data abstraction were conducted following PRISMA guidelines. Data extracted included the country/currency, perspective, clinical trial evidence, model structures, long-term efficacy extrapolation approaches (i.e., overall survival [OS]), time horizon, discount rates, and outcomes (i.e., life years [LY], quality-adjusted LY [QALY], and ICERs). The CEA model reported in Wakase et al. was updated using 5-year OS data from ELIANA and the CAR-T infusion rate informed by real-world practice. RESULTS: Sixteen records corresponding to 15 unique studies were included in the SLR (11 publications and 5 HTA reports); all were conducted from the health care system perspective of the respective countries. Most studies found tisagenlecleucel to be cost effective, but all studies' projected 3- and 5-year OS rates for tisagenlecleucel were lower than the observed 3- and 5-year rates, respectively, derived from 5-year ELIANA data. When applying updated OS projections from the most recent ELIANA data cut and higher infusion rates of 92.5% (per the real-world infusion rate)-96.0% (per the manufacturer success rate) to the CEA of Wakase et al., the associated QALYs for tisagenlecleucel increased from 11.6 to 14.6-15.0, and LYs increased from 13.3 to 17.0-17.5. Accordingly, the ICERs for tisagenlecleucel decreased from ¥2,035,071 to ¥1,787,988-¥1,789,048 versus blinatumomab and from ¥2,644,702 to ¥2,257,837-¥2,275,181 versus clofarabine combination therapy in the updated CEA model. CONCLUSIONS AND RELEVANCE: Projections at launch of the likely cost effectiveness of tisagenlecleucel appear to have underestimated its ultimate economic value given more recent trial and real-world data. To balance uncertainty in initial valuation with the need to provide access to novel oncology therapies, payers can consider flexible reimbursement policies alongside ongoing assessments as new data emerge.

Cost-effectiveness analysis of semaglutide 2.4 mg for the treatment of adult patients with overweight and obesity in the United States.

BACKGROUND: The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an anti-obesity medication (AOM) recently approved by the US Food and Drug Administration, has demonstrated clinically relevant weight loss in its phase 3 clinical trials. Economic evaluation comparing semaglutide 2.4 mg with other available weight management therapies is essential to inform payers for decision-making. OBJECTIVES: To assess the cost-effectiveness of semaglutide 2.4 mg in the treatment of adult patients with obesity (ie, body mass index [BMI] ≥ 30) and adult patients who are overweight (ie, BMI 27-29.9) with 1 or more weight-related comorbidities from a US third-party payer perspective. METHODS: A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Sensitivity analyses were conducted to test the robustness of the cost-effectiveness results to plausible variation in model inputs. RESULTS: In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained. In the sensitivity analysis, extended maximum treatment duration, types of subsequent treatment following therapy discontinuation, and weight-rebound rates were identified as key drivers for model results. The estimated probability of semaglutide 2.4 mg being cost-effective compared with comparators ranged from 67% to 100% when varying model parameters and assumptions. CONCLUSIONS: As a long-term weight management therapy, semaglutide 2.4 mg was estimated to be cost-effective compared with no treatment, D&E alone, and all other branded AOM comparators under a WTP threshold of $150,000 per QALY gained over a 30-year time horizon. DISCLOSURES: Financial support for this research was provided by Novo Nordisk Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Pediatric and Young Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia in Japan.

Until recently, treatment options were relatively limited for children and young adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). Tisagenlecleucel is a chimeric antigen receptor T cell (CAR-T) immunotherapy with promising efficacy and manageable safety that was approved in Japan in 2019 for the treatment of CD19-positive r/r B cell ALL (B-ALL). However, there is no publication assessing the cost-effectiveness of CAR-T in Japan. The objective of this study was to assess the cost-effectiveness of a tisagenlecleucel treatment strategy compared to a blinatumomab treatment strategy and a clofarabine combination treatment strategy (i.e., clofarabine + cyclophosphamide + etoposide) in Japan for pediatric and young adult patients up to 25 years of age with r/r B-ALL. A partitioned survival model with a lifetime horizon and monthly cycle was constructed from a Japanese public healthcare payer's perspective. Patients were distributed across the following partitioned health states: event-free survival (EFS), progressive disease, and death, which were informed by the EFS and overall survival (OS) data of respective clinical trials before year 5. For the tisagenlecleucel arm, a decision-tree structure was used to partition patients based on the infusion status; those who discontinued prior to receiving infusion were assigned efficacy and cost inputs of blinatumomab and those who received infusion were assigned efficacy and costs inputs based on tisagenlecleucel-infused patients. As trial data for blinatumomab and clofarabine ended before year 5, matching-adjusted indirect comparisons were used to extrapolate OS between the end of trial observation and up to year 5. All surviving patients followed the mortality risk of long-term ALL survivors without additional risk of disease relapse after year 5, regardless of initial treatment strategies. The model accounted for pretreatment costs, treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation costs, and terminal care costs. Incremental cost-effectiveness ratios (ICERs) per life-years (LYs) gained and ICERs per quality-adjusted life-years (QALYs) gained were evaluated using a 2% discount rate, and a threshold of ¥7.5 million was used to assess cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel, blinatumomab, and clofarabine combination treatment strategies were 13.3, 4.0, and 2.7 years, respectively; the corresponding QALYs were 11.6, 3.1, and 2.1 years, respectively. The ICERs per QALY gained for tisagenlecleucel were ¥2,035,071 versus blinatumomab and ¥2,644,702 versus clofarabine combination therapy. Extensive sensitivity analyses supported the findings. Tisagenlecleucel is a cost-effective treatment strategy for pediatric and young adult patients with r/r B-ALL from a Japanese public healthcare payer's perspective.