Juno Therapeutics Cancer Trial Stops After 3 Deaths, But Other Gene Therapy Trials Continue

The promising biotech field of CAR-T cell therapy got dealt a blow this week when the FDA put a stop to a clinical trial applying the treatment to leukemia patients. Xconomy reports that two of the patients died last week, following one participant who had died in May, triggering the intervention from the U.S. Food and Drug Administration.

Juno Therapeutics, the Seattle-based company behind the clinical trial, says that the deaths were each the result of cerebral edema, a serious condition in which excess fluid accumulates inside the brain. The company suspects that the addition of a chemotherapy drug, fludarabine, is responsible for the fatal side effect.

The trial of the JCAR015 treatment was in phase two, or mid-stage, which involves testing the therapy's effectiveness. Juno is asking the FDA to allow a continuation of the JCAR015 trial without fludarabine, but for now the agency is holding off on giving them the go-ahead, asking the company to present a revised trial protocol and submit other required materials.

JCAR015 is a form of cancer immunotherapy using gene-modified T lymphocytes, or T cells, which are key players in the immune system. T cells play vital parts in the body's mechanisms for fighting off disease.

The JCAR015 therapy involves extracting T cells from the patient's body and genetically modifying them to express chimeric antigen receptors (CARs) that can detect cancer-specific antigens. These bio-engineered CAR-T cells are then introduced to the body, where their task is to find and kill cancerous cells.

The phase 1 trial of JCAR015 showed great promise, with Juno reporting in December 2014 that 24 of 27 adult patients receiving the treatment had gone into remission, including six who remained cancer-free for more than a year. The patients were suffering from refractive acute lymphoblastic leukemia. As The Scientist notes, "This disease is extremely hard to treat and progresses rapidly when it becomes refractory; most patients die within a few months." Although the JCAR015 trial has been halted, Juno still has at least three other ongoing trials of CAR-T cell therapies.

The biotech industry is majorly invested in CAR-T cell therapy. "By now, most major pharmaceutical companies have jumped into the CAR T-cell arena," according to The Scientist, noting that the fledgling sector has seen a rise in scientific, corporate and investor interest beginning in late 2013.

Juno Therapeutics itself had raised $264.6 million when the company went public in 2014, the biggest biotech initial public offering of that year. But the current setback has caused the company's stock to drop, with the share price falling by 27 percent in the after-hours trading following the FDA-mandated shutdown, reports the New York Times.