ACT To Sustain: Adoptive Cell Therapy To Sustain Access to Non-Commercialized Genetically Modified Cell Therapies

Abstract

Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications. The American Society for Transplantation and Cellular Therapy (ASTCT) formed a task force named ACT To Sustain (Adoptive Cell Therapy to Sustain) to address the "valley of death" of academic GMCT products. This paper presents the task force's findings and considerations regarding financial sustainability of academically sponsored GMCT products in the absence of commercial development. We outline case scenarios illustrating barriers to maintaining access to promising GMCT developed by academic centers. The paper also delves into the current state of GMCT development, commercialization, and reimbursement, citing examples of abandoned products, cost estimates associated with GMCT manufacturing and real-world use of cost recovery. We propose potential solutions to address the financial, regulatory, and logistical challenges associated with sustaining access to academically sponsored GMCT products and to ensure that products with promising results do not languish in a "valley of death" due to financial or implementational barriers. The suggestions include aligning US Food and Drug Administration (FDA) designations with benefit coverage, allowing for cost recovery of certain products as a covered benefit, and engaging with regulators and policy makers to discuss alternative pathways for academic centers to provide access. We stress the importance of sustainable access to GMCT and call for collaborative efforts to develop regulatory pathways that support access to academically sponsored GMCT products.

Keywords: Academic sponsor; Access; Genetically modified cell therapies; Investigational.

Figure 1:

The interaction of academic and biopharma clinical development paradigm for new genetically modified cell therapies. Preclinical testing in an academic setting can yield a research IND used by the academic sponsor in early phase clinical trials to show proof of concept and early evidence of tolerability and efficacy. There is the potential for intellectual property (IP) from the academic sponsor to be licensed to a biopharma partner for commercialization at several points during development. The biopharma partner then submits a commercial IND for further clinical development which may ultimately lead to a commercial product if a successful BLA submission is granted FDA approval. However, in the absence of a biopharma partner, or at any time if the partner makes a decision to cease development and abandon the IP, products are shelved in what is termed the valley of death. In academia, there is often iterative development of successive GMCT based on the development of new technology combined with early data from clinical trials of an early generation GMCT which may also lead to a valley of death for promising products, limiting access to small numbers of participants in a clinical trial.

Figure 2.

Proposed new pathway for cost recovery to be aligned for research INDs, for potential financial sustainability. In the current state, there is no connection between FDA authorizing cost recovery and coverage policies allowing for reimbursement of investigational products. A proposed solution to this could be the creation of a specific designation to research INDs. If early clinical trial data demonstrates promising efficacy and tolerability, a review could occur by the FDA. In the ideal state, the amount of data required by FDA would be less onerous than what is required for a BLA submission. Once granted category B designation with FDA authorized cost recovery, the goal would be to work with payers to include specific language in their policies to allow for reimbursement of category B IND products, modeled after the investigation device development and precedent of CMS payment for category B IDE devices.