CAR-T at a crossroad as industry looks to allogeneic

As cell therapies move through the clinic towards commercialization, respondents to a KNect365 industry survey are beginning to look to allogeneic – or off-the-shelf – products as the next big thing.

Almost 200 people contributed to the Cell Therapy Analytics Report from KNect365, revealing their current position within the burgeoning cell and gene therapy space and offering up their thoughts and predictions for the future.

The majority worked within companies developing oncology products, and the largest group – 41% – said they are specifically developing chimeric antigen receptor (CAR) T-cell therapies. This developmental divulgence reflects the regulatory successes of Novartis’ Kymriah (tisagenlecleucel) and Kite/Gilead’s Yescarta (axicabtagene ciloleucel), both of which shook the drug world when approved in 2017.

Image: iStock/megatronservizi

Both Kymriah and Yescarta are made using a patient’s own cells, which are genetically engineered and then reinserted into the patient. These ‘autologous’ products require intricate manufacturing processes and a complex logistics network, leading to a very high cost of production and, naturally, a very large price tag. The two therapies have been listed at $373,000 and $475,000, respectively.

When asked where the next big success and/or approval will lie in the cell and gene therapy industry, 47% ticked the “gene therapy” box. This may be slightly misleading as several gene therapies have already been commercialized, the latest being AveXis/Novartis’ Zolgensma (onasemnogene abeparvovec) priced at $2.1 million, and while we are still in the early days of the industry.

A quarter checked “Solid Tumor treatment,” which makes more sense as the CAR-Ts available and about to breakthrough are all focusing blood cancers.

But more interesting is the written responses, with several stating allogeneic immunotherapies will be the next big thing in cell therapies.

Much talk has been on reducing the cost of goods for CAR-T therapies using technologies around automation and analytic, but the prospect of an allogeneic – or ‘off-the-shelf’ – CAR-T would alter the COGS concern with cell therapies. Large batch manufacturing will play into economies of scale, and with technologies available and well-established in the antibody industry, allogeneic therapies could recalibrate the sector back to a COGS model more appealing to healthcare providers and patients.

Companies have begun to focus on allogeneic CAR-Ts; Gilead/Kite has expressed its intentions to submit an Investigational New Drug (IND) request for an off-the-shelf product before the end of the year. And Allogene, with Pfizer backing, has already begun constructing a manufacturing facility for its allogeneic pipeline.

Download the full report here.