- Juno Therapeutics said Tuesday the Food and Drug Administration had lifted a clinical hold on a trial of the company's leading CAR-T therapy, which was abruptly halted last week after three patients died.
- Patient enrollment into the study, known as the "ROCKET" trial, will now continue after Juno revised its treatment protocol to avoid use of fludarabine, a chemotherapy agent thought to have led to the patient deaths.
- Juno will now use only cyclophosphamide pre-conditioning going forward. For pre-conditioning, patients are typically given a cocktail of chemo drugs before infusion of the CAR-T therapy.
Juno has been at the leading edge of developing CAR-T, along with rival biotech Kite Pharma and the Swiss drug giant Novartis. But the tragic deaths of three patients who had received treatment with Juno's lead candidate, known as JCAR015, had led to fresh concerns about the safety of new immunotherapies like CAR-T.
Juno was testing JCAR015 in patients with relapsed or refractory B cell acute lymphoblastic leukemia (ALL).
In CAR-T, a patient's immune cells are extracted and genetically engineered to better target cancerous cells. These immune cells, or T-cells, are then reintroduced back into the body. While early studies of CAR-T have shown promise in treating tough cancers, long-term safety is still somewhat of a question mark.
While Juno seemed confident that the addition of fludarabine was the culprit for the three deaths, the FDA's clinical hold looked like it would significantly delay further clinical development of JCAR015.
Now, in a rapid reversal, Juno has a green light to proceed with patient enrollment in its study. It is unclear what effect this might have for the company's plan to file the drug for FDA approval sometime next year.
Juno said it submitted to the FDA revised copies of its consent form, investigator brochure and trial protocol, along with a summary of a presentation it made to the regulator last week. The FDA accepted Juno's proposal to continue its trial with only cyclophosphamide as a pre-conditioning agent.
Hours after Juno had announced the hold last week, Kite said it had completed enrollment for a Phase 2 trial testing its own leading CAR-T therapy, known as KTE-C19. As Kite also uses fludarabine in its pre-conditioning regimen, some had taken the announcement's timing as a signal Kite was confident that the fatal interaction between the chemo drug and CAR-T therapy was unique to Juno's trial.
But even with Juno cleared to restart its trial, there is still a lot unknown about how fludarabine interacted fatally with JCAR015.
Speaking on CNBC Fast Money Tuesday, Juno CEO Hans Bishop said the company believed the toxicity was caused by the interaction between fludarabine and the CAR-T cells.
"Our view is not that this toxicity was caused exclusively by this second chemotherapy called fludarabine that we added. It is a combination of the strength of the chemotherapy we used with the cells," Bishop said.
Pointing to positive results from an earlier trial using cyclophosphamide alone, Bishop said he thought JCAR015 could still be an effective new treatment option for ALL.
"Losing patients on a clinical trial is always more than a blip in the road. It is a sobering experience. We are clearly figuring out how to best use these potent therapies," Bishop said on CNBC. "The promise of them, I think remains unchanged."
Juno stock jumped more than 25% in after-hours trading on Tuesday, while Kite was up by over 7%.