FDA puts 2seventy CAR-T trial on hold in wake of patient death

The FDA has put an early-phase trial of 2seventy bio’s CD33-targeted CAR-T cell therapy on hold in the wake of a patient death.

The trial’s investigators had already paused the trial in June following news that an acute myeloid leukemia patient, the first person treated by Seattle Children’s in the second dose cohort of the phase 1 study, had died. Since then, 2seventy and the hospital have been conducting an internal investigation to identify the cause of the fatality, the company said in a fourth-quarter earnings report.

“This investigation provided insights into the potential pathobiology of this toxicity which led to several study protocol changes, which the team believes may mitigate this toxicity and allow for the continuation of the PLAT-08 study,” the company said.

Still, on Aug. 11, the FDA emailed 2seventy to formally place the trial on hold, 2seventy revealed today.

The biotech and Seattle Children’s “will continue to work with FDA to provide the root cause analysis and proposed changes for the clinical study,” 2seventy said in this morning’s release. “Based on upcoming discussions with FDA, 2seventy bio and Seattle Children’s plan to amend the study accordingly and resume this study as soon as possible."

The paused clinical trial is the first time 2seventy has tested its drug-regulated CAR-T cell platform in humans, and the biotech was looking to the study to lay the foundation for future work on CD33 and solid tumor targets.

The bluebird bio oncology spinoff designed the therapy, dubbed SC-DARIC33, with a CAR architecture that physicians can turn on and off with another drug, namely rapamycin. Giving the drug at non-immunosuppressive dose levels activates the CAR-T cell therapy. When rapamycin is absent, the therapy is inactive, allowing hematopoietic cells to recover. 

2seventy began testing out this theory last year, when Seattle Children’s dosed the first patient with SC-DARIC33. The early signs looked good, with investigators reporting in May that infusions at the first dose level were generally well tolerated by the first three patients. None of the patients suffered dose-limiting toxicities. 

The biotech ended June with cash and equivalents of $307 million. Combined with revenue from the CAR-T therapy Abecma, for which it equally shares all the U.S. profits with Bristol Myers Squibb, 2seventy expects its financial runway to last into 2026.