Off-the-shelf CAR-T cell therapies have long been touted as a clear improvement over autologous treatments, which require a laborious and pricey manufacturing process. And now, leading off-the-shelf CAR-T treatments in the clinic are showing signs they could work just as well in different cancers as potential rivals like Yescarta from Gilead Sciences’ Kite Pharma and Breyanzi from Bristol Myers Squibb.
But the reality of bringing an off-the-shelf CAR-T to patients could prove trickier than simply replacing autologous options. Rather than going head to head against approved treatments, companies like Caribou Biosciences are instead looking to fill gaps in the market where they can carve out an edge.
Last month, Caribou presented new data from a phase 1 trial of vispa-cel, a single-dose, patient-ready option, showing its donor-derived treatment produced a progression-free survival rate of 17.1 months in B-cell non-Hodgkin lymphoma. By comparison, separate trials for Breyanzi and Yescarta showed progression-free survival rates of 14.8 months and 14.9 months, respectively. Caribous notched that win even though its patient population was sicker than those in trials for the other drugs, according to the biotech’s CEO and founder, Rachel Haurwitz.
Overall, some 82% of patients responded to the treatment and 67% saw a complete response with a safety profile that was largely similar to Breyanzi, she said.
Despite the encouraging results, the treatment still has to clear additional hurdles, including demonstrating its safety and long-term efficacy in a planned phase 3 trial that Haurwitz said the company is working to fund.
Still, the company isn’t necessarily looking to unseat market leaders. Caribou is targeting the more than 75% of patients who might benefit from CAR-T but can’t currently access it, she said.
The coming CAR-T showdowns
Caribou isn’t alone in its hunt to bring an off-the-shelf CAR-T to market, and its nearest competition is Allogene’s phase 2 option, cema-cel, which is targeting the same type of lymphoma.
Allogene is also focused on establishing its own niche.
Specifically, Allogene is positioning the investigational treatment as a tool to prevent cancer recurrence in high-risk patients who have undergone a standard first-line treatment regimen called R-CHOP. Patients in the Allogene trial either receive cema-cel following this initial treatment or are monitored for cancer recurrence. An interim futility analysis found that the treatment reduced more lingering cancer cells than untreated patients.
Haurwitz said that because vispa-cel could benefit a different patient population than cema-cel, there is space in the market for both.
Because vispa-cel eliminates many of the drawbacks of traditional CAR-T, including the need for apheresis, the procedure that collects T-cells from the blood, patients can get started on treatment immediately, Haurwitz said. That option could prove crucial for critically ill patients who often need bridging therapies when awaiting their individualized CAR-Ts.
That shift could reduce the costs related to vispa-cel by as much as 96% over autologous CAR-Ts, Haurwitz said, but she noted it’s still too soon to say what the treatment’s price would be if approved.
Vispa-cel could also improve availability by expanding treatment beyond limited specialized facilities, which can be challenging for some patients to access, and into more community-based treatment centers that are already administering complex therapies like bispecific antibodies.
“If you think about both bispecifics and allogeneic CAR-T, they are very similar in terms of their care needs, specifically around side effects and adverse events,” Haurwitz said.
These include neurotoxicity and cytokine release syndrome, a reaction that causes systemic inflammation.
“Both bispecifics and allogeneic CAR-T will result in some fraction of patients experiencing those,” she said, noting that having facilities close to home will help care providers monitor patients.
For now, Caribou is focused on moving vispa-cel into a pivotal phase 3 trial. But the timeline depends on when the company can secure the needed funding.
“There’s no magic date on the calendar,” Haurwitz said.
