The FDA has placed Kezar Life Sciences’ lupus trial on hold after the biotech flagged four deaths during the phase 2b study.
Kezar had been evaluating the selective immunoproteasome inhibitor zetomipzomib as a treatment for lupus nephritis. But the company revealed a week ago that it had suspended the study after a review of emerging safety data revealed the death of four patients in the Philippines and Argentina.
The PALIZADE study had enrolled 84 patients with active lupus nephritis, a kidney-disease-related complication of systemic lupus erythematosus, Kezar said at the time. Patients were dosed with either 30 mg or 60 mg of zetomipzomib or placebo and standard background therapy.
The plan was to enroll 279 patients in total with a target readout in 2026. But five days after Kezar announced the trial’s pause, the biotech said the FDA—which it had alerted about the deaths—had been back in touch to formally put the trial on hold.
A safety review by the trial’s independent monitoring committee's safety had already revealed that three of the four deaths showed a “common pattern of symptoms” and a proximity to dosing, Kezar said last week. Additional nonfatal serious adverse events showed a similar proximity to dosing, the biotech added at the time.
“We are steadfastly committed to patient safety and have directed our efforts to investigating these cases as we look to continue the zetomipzomib development program,” Kezar CEO Chris Kirk, Ph.D., said in the Oct. 4 release.
“At this time, our zetomipzomib IND for the treatment of autoimmune hepatitis is unaffected,” Kirk added. “Our Phase 2a PORTOLA clinical trial of zetomipzomib in patients with autoimmune hepatitis remains active, and we have not observed any grade 4 or 5 [serious adverse events] in the PORTOLA trial to date.”
Lupus remains a tricky indication, with Amgen, Eli Lilly, Galapagos and Roivant all suffering clinical failures over the past couple of years.
The pause in lupus plans is only the latest disruption for Kezar, which shrank its workforce by 41% and significantly trimmed its pipeline a year ago to save up enough cash to cover the PALIZADE readout. More recently, the company dropped a solid tumor asset that had originally survived the pipeline culls.
Even zetomipzomib has not been immune to the changes, with a phase 2 miss in a rare autoimmune disease derailing plans to pitch the drug as an inflammatory disease pipeline-in-a-product.