They say lightning rarely strikes twice but Kezar Life Sciences has suffered its second clinical blow in as many months. Image credit: Shutterstock / blentley

Kezar Life Sciences has been handed a second clinical hold by the US Food and Drug Administration (FDA) in as many months.

The FDA told the San-Francisco based biotech to halt the PALIZADE study (NCT05781750), a Phase IIb trial investigating zetomipzomib in patients with active lupus nephritis (LN), back in October. Yesterday (12 November) amongst its Q3 financials, Kezar announced that the FDA has now placed a partial clinical hold on its PORTOLA study (NCT05569759), a Phase IIa study investigating zetomipzomib in patients with autoimmune hepatitis.

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The company stock remained relatively stable following the announcement, with just a 3% drop at market open today compared with market close yesterday.

The PALIZADE trial was halted after four patients died in the trial, including one patient in the placebo cohort. No patient fatalities have been reported in the PORTOLA trial.

Following the October hold, Kezar terminated development of the candidate in lupus and concentrate efforts on autoimmune hepatitis patients. Kezar is unblinding the PALIZADE trial and will conduct a full investigation into all safety events from the study with data expected at a later date.

Originally, in October the Independent Data Monitoring Committee (IDMC) recommended that the PORTOLA trial proceed without modification. The IDMC examined safety data from all patients enrolled in the trial, including data from patients who completed the double-blind treatment period and continued to the open-label extension (OLE) portion of the trial.

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Following this, the FDA told Kezar that the last four patients enrolled in PORTOLA may continue in the double-blind portion of the study but cannot continue onto the OLE portion as part of the partial clinical hold. The patients who are currently participating in the OLE may continue treatment on zetomipzomib, but prednisone dosage may not be tapered below 5mg/day, and any patients who tapered below this amount will raise their prednisone back to 5mg/day.

Kezar’s CEO, Dr. Chris Kirk said: “We are working to understand the safety events that occurred in the PALIZADE trial in lupus nephritis, including deaths that occurred in both the placebo and drug arms, so that we can provide patients and physicians appropriate guidance during our ongoing and future clinical trials.”

PORTOLA is a placebo-controlled, randomised, double-blind study involving 24 patients with autoimmune hepatitis to evaluate whether zetomipzomib helps patients achieve complete biochemical response after 24 weeks. Kezar plans to report topline data in the first half of 2025.

In August, Kezar stopped development of its Phase I solid tumour drug KZR-261 to streamline focus on zetomipzomib.

Zetomipzomib is a novel, selective immunoproteasome inhibitor which targets the immunoproteasome subunit LMP7.