Short Time to Market and Forward Planning Will Enable Cell Therapies to Deliver R&D Pipeline Value

Abstract

There is considerable industry excitement about the curative potential of cell and gene therapies, but significant challenges remain in designing cost-effective treatments that are accessible globally. We have taken a modeling-based approach to define the cost and value drivers for cell therapy assets during pharmaceutical drug development. We have created a model development program for a lentiviral modified ex vivo autologous T cell therapy for Oncology indications. Using internal and external benchmarks, we have estimated the total out-of-pocket cost of development for an Oncology cell therapy asset from target identification to filing of marketing application to be $500-600 million. Our model indicates that both clinical and Chemistry Manufacturing and Controls (CMC) cost of development for cell therapies are higher due to unique considerations of ex vivo autologous cell therapies. We have computed a threshold revenue-generating patient number for our model asset that enables selection of assets that can address high unmet medical need and generate pipeline value. Using statistical approaches, we identified that short time to market (<5 years) and reduced commercial cost of goods (<$65,000 per dose) will be essential in developing competitive assets and we propose solutions to reduce both. We emphasize that teams must proactively plan alternate development scenarios with clear articulation of path to value generation and greater patient access. We recommend using a modeling-based approach to enable data driven go/no-go decisions during multigenerational cell therapy development.

Bayesian cell therapy process optimization

“…The required time and monetary investments are often disincentivized by high time-to-market pressures, costly clinical trials, and the complexity of the underlying biological mechanisms which are often not completely understood (Krishna et al, 2021;Silva et al, 2022).…”

“…Automation and closing of manufacturing processes are seen as key drivers for making cell therapies affordable and accessible to large patient populations (Abraham et al, 2021; Heathman et al, 2015). The required time and monetary investments are often disincentivized by high time‐to‐market pressures, costly clinical trials, and the complexity of the underlying biological mechanisms which are often not completely understood (Krishna et al, 2021; Silva et al, 2022). Thus, there is a need for process development tools that are effective, efficient, and do not require extensive mechanistic knowledge of the underlying biological processes.…”

“…However, the wide range of cell types and therapeutic modalities that are involved essentially requires the development of a somewhat customized process for each of these therapies. This involves a significant amount of process development and optimization, which is often disincentivized by costly clinical trials and high time‐to‐market pressures (Kasemiire et al, 2021; Krishna et al, 2021; Silva et al, 2022). In the case of biopharmaceuticals, these challenges have partially been mitigated through in silico process development with digital twins, although these approaches have not been successful for cell therapies so far (Kroll et al, 2017; Zobel‐Roos et al, 2021).…”

Identification of a small molecule for enhancing lentiviral transduction of T cells

“…For these reasons, large volumes of lentiviral vector are often required in the production of these therapies, which in turn increases the cost of manufacturing. 2 …”

Report on Webinar Series Cell and Gene Therapy: From Concept to Clinical Use

“…Breakdown of external project expenditure from a commitment to pivotal clinical trial to launch, adapted from[12].…”