Kezar Life Sciences went all in on its autoimmune candidate zetomipzomib after a restructuring last year. Now, the company has hit the brakes on its phase 2b study of the drug in lupus nephritis following four patient fatalities.
An independent data monitoring committee (IDMC) recommended suspending trial enrollment and dosing after a review of emerging safety data revealed the death of four patients in the Philippines and Argentina, Kezar said in a Monday press release.
The company's PALIZADE study had enrolled 84 patients with active lupus nephritis, a kidney disease-related complication of systemic lupus erythematosus. Patients were dosed with either 30 mg of zetomipzomib, 60 mg of zetomipzomib or placebo and standard background therapy.
The trial was intended to include a total of 279 patients, spanning 52 weeks, featuring a target readout in 2026.
The monitoring committee's safety review revealed that three of the four deaths showed a “common pattern of symptoms” and a proximity to dosing, according to Kezar. Additional non-fatal serious adverse events showed a similar proximity to dosing, the biotech said. The company remains blinded to the specific data on which patients were in the treatment or placebo arms.
Kezar is alerting regulatory agencies about its decision to pause the study while it reviews the data and decides on next steps. So far, the FDA hasn’t issued its own clinical hold on the trial.
“Our top priority is the safety of every patient who participates in our clinical trials,” Kezar CEO Chris Kirk, Ph.D., said in the release. “We will continue to work with the site investigators to learn more about each of these cases and hope to have an informed discussion with the IDMC and regulatory authorities as we look to continue the zetomipzomib development program in lupus nephritis and autoimmune hepatitis.
Kezar will provide further information regarding the investigation and the zetomipzomib development program “at the appropriate time,” Kirk added.
A phase 2a trial of the drug in autoimmune hepatitis is still active and has finished enrollment, with no severe adverse events recorded so far.
Last October, the San Francisco-based biotech cut its workforce by 41% and significantly trimmed its pipeline to save enough on costs to bring the PALIZADE readout to fruition. At the time, William Blair analysts called the move a “prudent decision given investors’ concerns about the ability of the company to complete the PALIZADE trial.”
More recently, the company dropped a solid tumor asset that had originally survived the pipeline culls.
Before zoning in on lupus and hepatitis, Kezar had initially pitched selective immunoproteasome inhibitor zetomipzomib as an inflammatory disease pipeline-in-a-product. That ambition was derailed after a phase 2 miss in rare autoimmune disease dermatomyositis or polymyositis.