Cell Therapy EconomicsPutting a price tag on novel autologous cellular therapies
Introduction
In the past decade, there has been a rapid increase in the development of autologous cell therapies, with several investigational products demonstrating encouraging clinical outcomes, especially in immunotherapies. It has been recognized, for instance, that adoptive transfer of in vitro expanded virus-specific T cells can prevent and also effectively treat viral infectious complications in immunocompromised patients after solid organ transplantation (SOT) or hematopoietic stem-cell transplantation (HSCT) [1], [2], [3], [4]. Infectious complications that arise due to immunosuppression, which organ recipients need for the lifetime of the transplanted organ to prevent rejection, are mainly caused by the cytomegalovirus (CMV), BK virus, and the Epstein-Barr virus (EBV) [5]. Although the adoption of universal antiviral prophylactic strategies has significantly reduced the incidence of CMV infection and disease, the development of drug-resistant and late-onset CMV disease after discontinuation of these prophylactic antivirals is prone to high risk of malignancy, graft loss and mortality [6], and associated with a significant increase in treatment costs [7]. Additionally, other serious adverse events such as nephrotoxicity and neutropenia can also result from the administration of anti-viral agents [8]. Thus, adoptive immunotherapies associated with lower toxicities for the prevention and treatment of CMV infection and disease are highly needed and may also produce overall cost savings in post-transplantation patient care. Indeed, a recent study has suggested that even if the prevention capabilities of anti-viral donor-derived cytotoxic T lymphocytes (CTL) in HSCT, which cost $10,000 to manufacture, would only be 50% effective at avoiding the need for antiviral treatment, it is still considered the less expensive option compared with the cost of anti-viral treatment and associated hospital care of more than $50,000 per patient [9]. Researchers working in this field anticipate that such therapies could replace conventional treatments, possibly allowing this novel therapeutic category to be accepted as standard practice [10]. However, if these products are to find their way into routine clinical practice, obvious hurdles associated with their lengthy development timelines, pricing, reimbursement and commercialization need to be addressed and overcome. We sought to identify and describe some of these challenges from the perspective of academic institutions developing these advanced therapies. We are also providing a relevant case study to illustrate a detailed measure of manufacturing costs of a CMV-specific T-cell immunotherapy.
Section snippets
Developing a tailored business model for cell therapies
Autologous cell therapies are patient-specific products that require a considerable degree of flexibility in their manufacturing process, while following the principles of Good Manufacturing Practice (GMP), as mandated by regulations [11] and guidelines [12]. Any business models developed for the commercialization of autologous therapies, therefore, differ substantially from those used for small molecule drugs or other biologics. To compete with small molecule pharmaceuticals on the market,
Identifying the key cost drivers in manufacturing cell therapies
The relevant manufacturing costs of cellular products can be broken down into direct (variable) and indirect (fixed) costs. Material, personnel costs and process validation costs are examples of direct costs that have a variable cost share, depending on the manufacturing volume. Preventive maintenance, amortization of facility and equipment capital purchases and environmental monitoring are examples of indirect costs and have a fixed cost share, independent of actual GMP facility use times for
Preparing for lengthy development timelines and stringent regulatory requirement
Due to the media attention that new cell therapy products attract, there is high public expectation for rapid availability of these therapies. In spite of that, developers who are keen on translating novel therapeutic strategies into the clinic need to be well-equipped financially to succeed in their efforts. Some larger commercial developers do not have any expectation of substantial revenue derived from these novel products; they instead rely on less advanced products that have a less
Reaching a successful reimbursement rate
Reimbursement of cell and gene therapies is currently one of the most debated topics in the adoption process of novel technologies into the medicinal products market. On the one hand, if developers fail to reach a reimbursement rate that covers their incurred expenses, the product as well as the business structure behind it will never be able to survive in the open market. On the other hand, offering cell and gene therapies as highly overpriced products will not help them to achieve commercial
A case study: CMV-specific T cells for adoptive immunotherapy
We performed a cost estimation of a CMV-specific T-cell therapy manufactured in an academic GMP facility using the previously indicated costing model (Table I, Table II). To the authors' knowledge, no similar costing data exist in the public domain for such autologous cell therapy products. The cost model was used to calculate the costs of manufacturing the cellular product using the recently developed whole protein-spanning overlapping peptide pool-based approach with CMVpp65 and IE-1 peptide
Acknowledgments
This work was partially supported by a DFG-grant: SFB-TR36, project A2. The authors declare no competing financial interests.
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