The FDA has placed a clinical hold on Kezar Life Sciences' Investigational New Drug (IND) application for zetomipzomib in the treatment of lupus nephritis (LN), following the company's voluntary suspension of enrollment and dosing in its Phase 2b PALIZADE clinical trial. The decision was prompted by safety concerns, including four Grade 5 (fatal) serious adverse events (SAEs) observed during the trial.
The PALIZADE trial, a randomized, double-blind Phase 2b study, was evaluating two dose levels (30 mg and 60 mg) of zetomipzomib compared to placebo in patients with active LN. The trial's Independent Data Monitoring Committee (IDMC) recommended the suspension after reviewing emerging safety data from patients enrolled in the Philippines and Argentina.
The IDMC's review indicated that three of the fatalities shared a pattern of symptoms and occurred close to the time of dosing. Additional non-fatal SAEs also displayed a similar timing about dosing. Kezar remains unaware of which patients received zetomipzomib or the placebo.
Kezar's Response and Future Plans
Chris Kirk, PhD, Kezar’s Chief Executive Officer, stated, "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." The company is working with site investigators to gather more information about each case and plans to have discussions with the IDMC and regulatory authorities.
Kezar has informed all study investigators and is in the process of notifying regulatory authorities, including the FDA. The FDA will provide Kezar with an official clinical hold letter within 30 days.
Unaffected Programs
Kezar clarified that the clinical hold does not affect its zetomipzomib IND for the treatment of autoimmune hepatitis. The Phase 2a PORTOLA clinical trial of zetomipzomib in patients with autoimmune hepatitis remains active, and no Grade 4 or 5 SAEs have been observed in the PORTOLA trial to date.
About Lupus Nephritis
Lupus nephritis is a severe complication of systemic lupus erythematosus (SLE), affecting approximately 50% of SLE patients within 10 years of diagnosis. It is characterized by vascular, glomerular, and tubulointerstitial lesions and is associated with increased morbidity, including a higher risk of end-stage renal disease requiring dialysis or renal transplantation, and an increased risk of mortality. Current treatment options for LN are limited, typically consisting of induction therapy to achieve remission and long-term maintenance therapy to prevent relapse.
