Allogene makes ‘bold’ pivot, stopping pivotal trials in pursuit of first-line CAR-T cures

Nobody can accuse Allogene Therapeutics of lacking confidence. Believing that its CAR-T can boost cure rates, and thereby potentially make later-line treatment “obsolete,” the biotech has stopped two trials in advanced lymphoma patients to focus on a new study in people with minimal residual disease (MRD).

In 2022, Allogene began a pivotal trial of its off-the-shelf anti-CD19 CAR-T therapy in patients who have relapsed or refractory large B cell lymphoma after at least two lines of chemotherapy. The biotech added a second trial in the same patient population last year. Now, Allogene has pivoted, halting the two trials to focus development of the candidate on another opportunity.

Allogene’s idea is to make the CAR-T the seventh cycle of standard frontline treatment for lymphoma patients who have MRD after six cycles of chemotherapy. Today, physicians monitor patients after the sixth cycle, knowing that around 30% of patients will relapse but lacking the tools to intervene.

The belief that the CAR-T cemacabtagene ansegedleucel (cema-cel) is the tool physicians need is built on two factors. First, “cema-cel could be immediately accessible in community cancer centers following treatment with standard [chemotherapy combination] R-CHOP to boost cure rates, potentially rendering late-line treatment obsolete,” Allogene CEO David Chang, M.D., Ph.D., said on a call with investors.

That immediate availability differentiates cema-cel, formerly known as ALLO-501A, from autologous cell therapies. Cema-cel has always had that potential advantage over existing CD19 CAR-Ts. What changed, in Chang’s telling, is that Foresight Diagnostics developed a test for identifying patients with MRD. The test is the second factor.  

“I wish that we could have made a decision earlier except that the assay ... to diagnose these patients who are MRD positive, the sensitivity and the specificity of the assay was not quite at the level until Foresight introduced the assay. This is what's really enabling us to really take the right course of action with cema-cel,” Chang said.

The availability of the assay has enabled Allogene to design a pivotal trial focused on patients who have MRD after chemotherapy. Allogene plans to enroll 230 people to receive cema-cel or current standard of care and to assess event-free survival. The pivot could ease Allogene’s enrollment challenges by moving it into territory that is free from rival drug developers competing for the same set of patients. 

Chang said the newly targeted market “far exceeds” the opportunities “that currently exist in the second or the third line setting.” If Allogene is right, cema-cel will further diminish the later-line opportunities by increasing the first-line cure rate. 

Investors are unconvinced, but Allogene found some support for its pivot. Shares in Allogene fell 22% to $2.63 in premarket trading in the aftermath of the news. Support came from analysts at William Blair, who called Allogene’s new plan a “bold strategic pivot” that could enable the company to leapfrog rivals and “expand its total addressable market.”

“We believe allogeneic therapies are uniquely suited to be used as a frontline consolidation agent as they are more readily available than autologous products and more potent than bispecifics. Overall, we view Allogene’s cema-cel as a first-in-class and best-in-class therapeutic that could address multiple unmet needs in the treatment landscape,” the analysts wrote in a note to investors.