Towards sustainability and affordability of expensive cell and gene therapies? Applying a cost-based pricing model to estimate prices for Libmeldy and Zolgensma

Thielen, Frederick W.; Heine, Renaud; Berg, Sibren van den; Ham, Renske M.T. ten; Groot, Carin A. Uyl–de

doi:10.1016/j.jcyt.2022.09.002

Cited by 10 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Atidasagene autotemcel is one of the most expensive therapies, at about 3 million EUR per treatment. 35 This can pose a substantial financial burden to families receiving the treatment. Given that LV treatments are becoming increasingly mainstream as a highly effective treatment strategy, we must strongly consider making our vectors more competitive for widespread and affordable implementation.…”

Section: Discussionmentioning

confidence: 99%

Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations

Tricoli,

Sase,

Hacker

et al. 2024

Preprint

View full text Add to dashboard Cite

Metachromatic leukodystrophy (MLD) is a fatal lysosomal storage disease (LSD) characterized by the deficient enzymatic activity of arylsulfatase A (ARSA). Combined autologous hematopoietic stem cell transplant (HSCT) with lentiviral (LV) based gene therapy has great potential to treat MLD. However, if enzyme production is inadequate, this could result in continued loss of motor function, implying a high vector copy number (VCN) requirement for optimal enzymatic output. This may place children at increased risk for genomic toxicity due to higher VCN. We increased the expression of ARSA cDNA at single integration by generating novel LVs, optimizing ARSA expression, and enhancing safety. In addition, our vectors achieved optimal transduction in mouse and human HSC with minimal multiplicity of infection (MOI). Our top-performing vector (EA1) showed at least 4X more ARSA activity than the currently EU-approved vector and a superior ability to secrete vesicle-associated ARSA, a critical modality to transfer functional enzymes from microglia to oligodendrocytes. Three-month-oldArsa-KO MLD mice transplanted withArsa-KO BM cells transduced with 0.6 VCN of EA1 demonstrated behavior and CNS histology matching WT mice. Our novel vector boosts efficacy while improving safety as a robust approach for treating early symptomatic MLD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations

Tricoli,

Sase,

Hacker

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The lack of transparency from pharmaceutical companies regarding R&D expenses and the costs of drug manufacturing 42 is here emphasized as one limitation for the application of the model. 58 Moreover, as other authors have already pointed out, when R&D costs are calculated, they can be overestimated if the contribution of external research from large public academic medical centers with public funding and subsidies to companies are not taken into account. 49 In connection with this issue, it is worth mentioning that >50% of clinical trials with ATMPs and regenerative medicines worldwide are currently sponsored by academic and government institutions.…”

Section: Proposals To Address the Risks Arising From The Commodificat...mentioning

confidence: 99%

“…A cost-based pricing model developed for cancer drugs 57 has recently been applied for ATMPs in order to make compatible a fair profit for companies with sustainability and affordability. 58 According to the model, the price is based on the costs of research and development (R&D)—adjusted for risk of failure and cost of capital—drug manufacturing, sales, marketing, the eligible patient population during patent protection, and a reasonable profit margin for the industry linked to the level of clinical benefit. Applying this model, the prices could be set between a third and a fifth of the current ones in the examples analyzed.…”

Section: Proposals To Address the Risks Arising From The Commodificat...mentioning

confidence: 99%

Addressing Risks Derived From the Commodification of Substances of Human Origin: A European Proposal Applicable Worldwide

Cuende

Vilarrodona

Vuelta³

et al. 2023

Transplantation

View full text Add to dashboard Cite

In view of the public consultation recently launched by the World Health Organization on Regulatory Convergence of Cell and Gene Therapy Products and the Proposal for a Regulation on substances of human origin (SoHO) repealing the European Union Directives on Blood and on Tissues and Cells, an opportunity arises to define an ethical and transparent framework of collaboration between industry and authorities responsible for SoHO-derived products, comprising medicines, medical devices, transfusion, and transplantation. The commodification of SoHO-derived medicinal products and medical devices entails important risks to the sustainability of healthcare systems and threatens the equitable access of patients to innovative therapies. It may also jeopardize the principle of altruistic donation of SoHO that is required for the treatment and survival of thousands of patients every year. This article puts forward several proposals aimed at reconciling the ethical principles of voluntary and unpaid SoHO donation and the noncommercialization of the human body with obtaining a profit that allows business activities, while ensuring high quality, safety, and efficacy standards of tissues and cells for clinical use.

show abstract

“…Cell therapies are changing the treatment paradigm in cancer. Currently, the manufacturing processes to produce these therapies mainly consist of manual and open processing steps, confining the operations to high‐grade cleanrooms in the hands of specialized operators, which prevents them from addressing large patient populations at a sustainable price (Abraham et al, 2021; Fritsche et al, 2020; Harrison et al, 2017; Heathman et al, 2015; Szkodny & Lee, 2022; Thielen et al, 2022). Closing and automating these manufacturing processes can increase their scalability, and lower manufacturing costs by up to 50% (Breig & Luti, 2021b; Emerson & Glassey, 2021; McCoy et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Bayesian cell therapy process optimization

Claes,

Heck,

Coddens

et al. 2024

Biotech & Bioengineering

View full text Add to dashboard Cite

Optimizing complex bioprocesses poses a significant challenge in several fields, particularly in cell therapy manufacturing. The development of customized, closed, and automated processes is crucial for their industrial translation and for addressing large patient populations at a sustainable price. Limited understanding of the underlying biological mechanisms, coupled with highly resource‐intensive experimentation, are two contributing factors that make the development of these next‐generation processes challenging. Bayesian optimization (BO) is an iterative experimental design methodology that addresses these challenges, but has not been extensively tested in situations that require parallel experimentation with significant experimental variability. In this study, we present an evaluation of noisy, parallel BO for increasing noise levels and parallel batch sizes on two in silico bioprocesses, and compare it to the industry state‐of‐the‐art. As an in vitro showcase, we apply the method to the optimization of a monocyte purification unit operation. The in silico results show that BO significantly outperforms the state‐of‐the‐art, requiring approximately 50% fewer experiments on average. This study highlights the potential of noisy, parallel BO as valuable tool for cell therapy process development and optimization.

show abstract

Towards sustainability and affordability of expensive cell and gene therapies? Applying a cost-based pricing model to estimate prices for Libmeldy and Zolgensma

Cited by 10 publications

References 51 publications

Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations

Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations

Addressing Risks Derived From the Commodification of Substances of Human Origin: A European Proposal Applicable Worldwide

Bayesian cell therapy process optimization

Contact Info

Product

Resources

About