Economic Evidence on Potentially Curative Gene Therapy Products: A Systematic Literature Review

Ho, Joseph Khoa; Borle, Kennedy; Dragojlovic, Nick; Dhillon, Manrubby; Kitchin, Vanessa; Kopac, Nicola; Ross, Colin; Lynd, Larry D.

doi:10.1007/s40273-021-01051-4

Cited by 8 publications

(6 citation statements)

References 42 publications

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“…This real-world cost analysis covers a growing concern on health systems, the burden of expenses related to CAR T-cell therapies. CAR T-cells appear to provide significant clinical benefit despite their high cost, thus making economic evaluations highly relevant to support policymakers in reimbursement decisions [20,22,23,29,30]. The relevance of this study should be also viewed in the light of continuously evolving indications for this therapy [11,17,[31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…However, not all CAR T-cell therapeutic regimens were cost effective at standard cost-effective thresholds. Specifically, these therapies shown to be more cost effective in conditions with significant risk of mortality and/or disability [20]. The very high cost of CAR T-cells has raised concerns for patient access to these therapies, and the financial sustainability of healthcare systems, and it has been argued that substantial price reductions, or price payment only for initial complete response (at current prices), is required to improve axi-cel and tisa-cel cost effectiveness [41].…”

Section: Plos Onementioning

confidence: 99%

“…Nevertheless, substitution effects may reduce the financial impact or CAR T-cell therapy, avoiding current futile treatments, potentially reducing autologous and allogenic stem cell transplantation for relapsed patients. Formal assessment of these aspects will improve knowledge about this technology, effective economic evaluation and understanding its real cost [11,19,20].…”

Section: Introductionmentioning

confidence: 99%

“…To date, scarce research has quantified real costs attributable to CAR T-cell therapy, which is crucial in drug reimbursement discussion between health players. Country-specific economic evaluations are necessary to determine whether and how to offer patients these highly personalized forms of immunotherapy [11,[20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center

et al. 2022

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Real world effectiveness, toxicity and costs analyses from chimeric antigen receptor (CAR)-T cell therapy are of utmost relevance to determine whether and how to offer patients highly personalized immunotherapy. In this study, we aimed at describing CAR T-cells effectiveness, safety and costs in a Portuguese Comprehensive Cancer Center. We performed a retrospective descriptive study of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma referred to CAR T-cell therapy, between May 2019 and February 2021. Rates of treatment response, toxicity and survival (Kaplan-Meier method) were analyzed by intention-to-treat. Direct medical costs stratified by inpatient-care, outpatient-care, and diagnostic-therapeutic procedures (DTP) were derived based on resources used and their respective unit costs. In twenty patients (median age 49.5y; 55%male; 70%DLBCL; 50% with primary refractory disease), best overall and complete response rates were 65.0% and 45.0%, respectively. Median overall (OS) and progression-free survivals were 9.2 and 7.3 months; 12-month OS rate was 42.6% (95%CI:23.2–78.3). Grade≥3 cytokine release syndrome and neurotoxicity occurred in 5.6% and 11.1% of patients, respectively. CAR T-cell therapy expenditure, including adverse events costs, was 7 176 196€, or 286 238€ when excluding drug cost. Median cost for treated patient was 355 165€ with CAR T-cell drug cost accounting for 97.0% of the overall expense. Excluding CAR T-cell acquisition cost, inpatient-care and DTP accounted for 57% and 38% of total cost/patient, respectively. Our findings highlight the heavy economic burden of CAR T-cell therapy driven by drug acquisition costs.

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Section: Discussionmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center

et al. 2022

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“…For example, Strimvelis ® , a gene therapy treatment for severe combined immunodeficiency, will cause the incremental cost-effectiveness ratios when compared with hematopoietic stem cell transplants (hematopoetic stem cell transplant-haploidentical donor or hematopoietic stem cell transplant-matched unrelated donor) about £36,360 and £14,645 per quality-adjusted life-year, respectively ( South et al, 2019 ). Although with the higher cost, potentially curative gene therapy offers the possibility of lifelong benefits from a single course of treatment, which could lead to these therapies being more cost-effective than current treatments in the long term ( Ho et al, 2021 ). Therefore, the cost-effectiveness of gene therapy should be carefully considered from clinical trials to clinical practice ( Jayasundera et al, 2022 ).…”

Section: Gene Therapy Of Refractory Hypercholesterolemiamentioning

confidence: 99%

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

2022

Front. Genet.

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Refractory hypercholesterolemia (RH), including homozygous familial hypercholesterolemia (HoFH) and compound heterozygous familial hypercholesterolemia, is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) despite existing cholesterol-lowering methods at maximal tolerable doses. Patients with RH have early onset and higher risk of atherosclerotic cardiovascular disease (ASCVD) under insufficient treatment. Therefore, it is urgent to seek new therapies to maintain the blood lipids in refractory hyperlipidemia at normal levels. Currently, new cholesterol-lowering strategies are on the market, not only at the protein level [i.e., bempedoic acid (inhibiting ATP-citrate lyase), alirocumab and evolocumab (monoclonal antibodies against PCSK9), evinacumab (monoclonal antibody against ANGPTL3)] but also at the transcript level [i.e., mipomersen (antisense oligonucleotide inhibiting ApoB), inclisiran (siRNA targeting PCSK9)], providing more options for RH patients to achieve their lipid-lowering targets. More RNA-based therapies targeting RH-related genes have been designed for the treatment. However, for a proportion of patients, especially those with LDLR deficiency, the available treatments are still insufficient. More recently, emerging genome engineering based on CRISPR/Cas9 techniques, and advanced delivery technologies such as lentiviral vectors, adenoviral vectors, adeno-associated viral vectors, lipid nanoparticles, and exosomes are being rapidly developed and implemented as novel therapies for RH. Gene therapy targeting RH-related genes has been successfully conducted in cells, mice, and non-human primates with high efficacy in lipid lowering and good tolerability. Especially the new generation of genome editing technique, base editing, performed in vivo with ideal lipid-lowering effect and limited occurrence of unwanted results. Excitingly, a phase I/II clinical study of LDLR gene replacement has been recently completed in RH patients, likely to be employed in clinical practice in the future. Furthermore, new targets for cholesterol reduction such as REV-ERB, G protein-coupled receptor, Ubiquitin specific peptidase 20 are continually being developed. This narrative review updates recent advances in treatment for RH, summarizes related clinical trials and preclinical studies, especially on the prospect of gene therapy.

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Capturing the Impact of Constraints on the Cost-Effectiveness of Cell and Gene Therapies: A Systematic Review

et al. 2023

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Objective: Decision-makers need to resolve constraints on delivering cell and gene therapies to patients as these treatments move into routine care. This study aimed to investigate if, and how, constraints that affect the expected cost and health consequences of cell and gene therapies have been included in published examples of cost-effectiveness analyses (CEAs). Method:A systematic review identified CEAs of cell and gene therapies. Studies were identified from previous systematic reviews and by searching Medline and Embase until 21-January-2022. Constraints described qualitatively were categorised by theme and summarised by a narrative synthesis. Constraints evaluated in quantitative scenario analyses were appraised by whether they changed the decision to recommend treatment.Results: Thirty-two CEAs of cell (n=20) and gene therapies (n=12) were included. Twentyone studies described constraints qualitatively (70% cell therapy CEAs; 58% gene therapy CEAs). Qualitative constraints were categorised by four themes: single payment models; longterm affordability; delivery by providers; manufacturing capability. Thirteen studies assessed constraints quantitatively (60% cell therapy CEAs; 8% gene therapy CEAs). Two types of constraint were assessed quantitatively across four jurisdictions (USA, Canada, Singapore, The Netherlands): alternatives to single payment models (n=9 scenario analyses); improving manufacturing (n=12 scenario analyses). The impact on decision-making was determined by whether the estimated incremental cost-effectiveness ratios crossed a relevant costeffectiveness threshold for each jurisdiction (outcome-based payment models: n=25 threshold comparisons made, 28% decisions changed; improving manufacturing: n=24 threshold comparisons made, 4% decisions changed). Conclusion:The net health impact of constraints is vital evidence to help decision-makers scale up the delivery of cell and gene therapies as patient volume increases and more advanced therapy medicinal products are launched. CEAs will be essential to quantify how constraints affect the cost-effectiveness of care, prioritise constraints to be resolved, and establish the value of strategies to implement cell and gene therapies by accounting for their health opportunity cost. Key Points1. Decision-makers across health care systems need to resolve constraints on delivering cell and gene therapies as they move into routine care settings.2. The cost-effectiveness of cell and gene therapies can change if constraints impact the expected cost or expected health consequences of care.3. Robust evidence from cost-effectiveness analyses will help decision-makers identify the most valuable ways to resolve capacity and organisational constraints, improve access to advanced therapies, and maximise population net health benefit.

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Economic Evidence on Potentially Curative Gene Therapy Products: A Systematic Literature Review

Cited by 8 publications

References 42 publications

Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center

Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center

The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy

Capturing the Impact of Constraints on the Cost-Effectiveness of Cell and Gene Therapies: A Systematic Review

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