- Shares in Kite Pharma fell by as much as 13% Monday morning after the biotech reported a patient receiving its experimental CAR-T therapy axi-cel died from cerebral edema, resurfacing worries about fatal side effects tied to the emerging class of cancer treatments.
- Kite has informed the Food and Drug Administration of the death, which occurred at the end of April, and there has been no halt or pause to the ongoing safety expansion phase of Kite's ZUMA study.
- Cerebral edema has become a key safety concern surrounding CAR-T after the condition led to the deaths of five patients in rival Juno Therapeutics' study of its once lead candidate JCAR015. Juno eventually shuttered that program, dropping well behind Kite and Novartis in the push to win FDA approval for a CAR-T cell therapy.
After Kite successfully completed its filing for approval of axi-cel with the FDA in late March, analyst and market attention had shifted to the biotech's commercialization plans and manufacturing ramp-up ahead of a potential green light from the regulator.
But the patient death clearly rattled investors Monday, and brings safety concerns back to the forefront of the conversation around CAR-T therapy — which has dazzled with impressive clinical results but also can trigger neurological and immune-related side effects.
While Juno was forced to drop JCAR015 after unsuccessfully modifying its treatment regimen, Kite had so far been able to avoid any fatal brain swelling in the clinical testing of axi-cel.
"This was the first grade 5 [death] cerebral edema event that has occurred in approximately 200 patients who have been treated in the ZUMA clinical trials," Kite reported in a quarterly filing with the Security and Exchange Commission.
If studies conducted by the National Cancer Institute are included, more than 300 patients have been treated with axi-cel.
The patient in question had refractory non-Hodgkin lymphoma that was rapidly progressing at the time of enrollment, said Kite's Chief Medical Officer David Chang on a call with analysts Monday.
Chang said the patient's underlying condition and "extremely high" baseline levels of inflammation markers were Kite's initial focus in its review. Roughly two days of progressively worsening neurological events elapsed before the patient's death.
The death occurred in a safety expansion cohort which was initiated in September 2016 to evaluate an "adverse mitigation strategy" that involved giving patients levetiracetam and Actemra (tocilizumab) prophylactically. Thirty patients were treated in the U.S. arm of the cohort.
Three other deaths not due to disease progression have so far been recorded in the primary analysis of the pivotal ZUMA-1 trial testing axi-cel, two of which were judged to be related to treatment. None involved cerebral edema.
Reported rates of cytokine release syndrome and adverse neurological events associated with axi-cel — two other closely watched safety issues — have fallen since initial interim data from ZUMA-1 was released last September. Investigators in the study attributed the decline to improved management of CAR-T treatment and its side effects among physicians.