The Potential for CAR-Ts in Large Patient Populations

Cell and gene therapies (CGTs) are currently in use for small patient populations to either treat a rare disease or as a single-patient, single-dose treatment, but the biopharma industry is seeking ways to apply CGTs to mass patient populations. BioPharm International® spoke to David Chang, MD, PhD, president, CEO, and co-founder of Allogene Therapeutics, to gain a better understanding of how application to a mass patient population could work.

BioPharm: What are the most challenging hurdles in bringing CGTs market?

Chang (Allogene): As we move CAR-T [chimeric antigen receptor T cell] therapies into earlier lines of treatment, we’re presented with a significant opportunity, as patients are generally more responsive at these stages. However, this shift also brings new challenges, particularly in terms of delivery infrastructure. Most autologous CAR-T treatments are currently delivered in academic centers, yet most patients, especially those in earlier lines, are treated in community settings.

These community cancer centers do not have in place the complex infrastructure and resources required to administer autologous CAR-T therapies and often do not refer patients to academic centers for treatment. In fact, about 80% of patients are treated in the community cancer center setting. We believe this disconnect between where patients are treated and where CAR-T therapies are available represents a significant access barrier.

In contrast, cemacabtagene ansegedleucel (cema-cel, an investigational allogeneic cell therapy product) is designed to bypass many of the challenges that have hindered the adoption of autologous CAR-T therapies. Use of cema-cel shouldn’t require the complex logistics that have hindered CAR-T adoption, nor should there be a reliance on referrals as the intent is for CAR-T therapies to be available in these community cancer centers. These community physicians have been waiting for a product that is off-the-shelf, easily administered, and readily available on demand to bring CAR-T into their centers, and we believe cema-cel will meet these criteria.

BioPharm: What is the reality that a CGT can be applied to a mass patient population?

Chang (Allogene): We see significant potential for CAR-T in larger patient populations, but this can only be done by using an allogeneic product. The move into earlier lines of blood cancers, solid tumors, and autoimmune disease represents a significant expansion in the number of patients who could potentially benefit from these therapies. However, this also brings new challenges in terms of scalability.

Autologous CAR-T therapies have inherent limitations due to their complex logistics and bespoke manufacturing process, none of which is easily scalable. In fact, despite the commercial availability of autologous therapies since 2017, only about 10% of patients receive treatment today based on reported sales. To make CAR-T available where patients are treated, we need a different playbook.

Cema-cel [is an example of a product that] offers a potentially promising solution with a safety profile comparable to approved autologous CAR-T therapies. Made from healthy donor cells, cema-cel is designed to be produced in large batches that could treat up to 100 patients from a single manufacturing run. This ‘off-the-shelf’ approach, which also opens the door to use in community cancer centers where the majority of patients are treated, could significantly increase the scalability of CAR-Ts, bringing us one step closer to making this modality available to larger patient populations.

BioPharm: Do the biggest opportunities for mass application rely on Big Pharma, smaller biotechs, or other?

Chang (Allogene): The development and commercialization of CGTs represent a dynamic and rapidly evolving landscape. Both Big Pharma and emerging biotechs play crucial roles in driving innovation. Each brings unique strengths—Big Pharma with its extensive resources, commercialization expertise, and global reach, and biotechs with their agility and singular focus.

We’ve seen how biotechs can drive innovation in CGT. For instance, recogni[tion] of the increasing difficulties [faced by] autologous CAR-Ts in penetrating community cancer centers and accessing earlier line patients led us to quickly shift Allogene’s clinical development of cema-cel to explore its use in first line (1L) consolidation for newly diagnosed large B-cell lymphoma (LBCL) patients who are likely to relapse.

This led to the design of a new clinical trial (ALPHA3) that leverages an investigational diagnostic test developed by Foresight Diagnostics that detects the presence of minimal residual disease (MRD). When administered following completion of 1L treatment for LBCL, this test has the potential to offer a highly accurate prediction of future disease relapse. We believe this test could provide the ability to identify patients who are most likely to relapse after initial treatment with chemoimmunotherapy and enable physicians to take action (e.g., administer a single dose of investigational cema-cel) to prevent relapse.

This type of pivot would likely be unheard of in a bigger organization, but because of our size we were quickly able to adjust our strategy and refocus our resources. It’s this kind of innovative thinking and agility that will be key to democratizing cell therapy.

BioPharm: What partnerships or consortiums facilitate access to CGTs?

Chang (Allogene): As a clinical development company, we’re still in the early stages of exploring partnerships. We know physicians in community cancer settings are eager for an allogeneic product (such as cema-cel). We’re excited about the prospect of offering CAR-T more broadly and will be exploring ways to facilitate access in the coming years.

About the author

Feliza Mirasol is the science editor for BioPharm International.

Article details

BioPharm International®
Vol. 37, No. 7
July/August 2024
Page: 13

Citation

When referring to this article, please cite it as Mirasol, F. The Potential for CAR-Ts in Large Patient Populations. BioPharm International 2024, 37 (7), 13.