- Juno Therapeutics, a leading company in the race to develop a type of immunotherapy called CAR-T, on Thursday said the Food and Drug Administration had halted a clinical trial after two patients died from treatment last week.
- A third patient had died earlier from cerebral edema, but researchers originally thought the death was unrelated to the treatment, reports Forbes.
- The patients were enrolled in a trial testing a therapy called JCAR015, which is aimed at treating relapsed or refractory B-cell acute lymphoblastic leukemia in adults. Juno had hoped to file for U.S. approval of JCAR015, its leading CAR-T treatment, sometime next year.
The clinical hold on JCAR015 is a damaging blow to Juno and casts a tragic shadow over what has been seen as a promising new immunotherapy. A number of other companies, including Kite Pharma and Novartis, are also developing CAR-T treatments.
Juno said the patient deaths followed the addition of chemotherapy drug fludarabine to a treatment regimen aimed at preparing patients for the CAR-T therapy.
During CAR-T treatment, patient's immune cells are removed, genetically engineered to better target cancerous cells, and then reinserted into the body to attack the cancer. In Juno's trial, patients were given a number of chemotherapy drugs to kill off a patient's own T-cells before initiating the CAR-T therapy. This gives the engineered cancer-killing cells a better chance of growing in the body.
But adding in fludarabine seems to have reacted fatally with JCAR015, leading to the full clinical hold from the FDA after the three deaths.
Juno says it has proposed to the FDA to continue the JCAR015 trial by using another chemo agent, cyclophosphamide, and discontinuing use of fludarabine. The FDA has asked Juno to submit a revised patient consent form, along with a new investigator brochure and trial protocol. Juno will comply with the request this week, the company said.
According to a federal database for clinical trials, Juno had planned to enroll 90 patients in the trial, which was expected to be completed in December.
At minimum, the clinical hold will set back Juno's plans for next year and tarnish the glowing optimism around the potential for CAR-T therapies to revolutionize treatment of certain B-cell cancers. But the deaths could also more widely impact the CAR-T space, drawing more scrutiny to the effects of engineering human immune cells.
Juno stock plummeted by nearly 30% in after-hours trading, while rival Kite dropped by over 10%.