Kezar says interim study required by FDA would delay future zetomipzomib trials

Kezar Life Sciences (KZR) announced regulatory updates and the initiation of a process to explore a full range of strategic alternatives focused on maximizing shareholder value. The company has retained TD Cowen to support it with the strategic review process. Kezar has been unable to align with the Food and Drug Administration on a potential registrational clinical trial of zetomipzomib, a novel, selective inhibitor of the immunoproteasome, in patients with relapsed and refractory autoimmune hepatitis. The FDA Division of Hepatology and Nutrition cancelled a Type C meeting that was previously scheduled with Kezar in the fourth quarter to discuss a proposed study in AIH. Autoimmune hepatitis is a rare, chronic disease that if left untreated, can lead to cirrhosis, liver failure and hepatocellular carcinoma. In the United States, AIH affects approximately 100,000 individuals, predominantly women. There are no FDA-approved therapeutics for AIH and few industry-sponsored clinical trials. Current therapy involves life-long use of corticosteroids and immunosuppressive agents, which results in an increased risk of infections, malignancies, diabetes, osteoporotic fractures and cataracts. In March 2025, Kezar reported positive safety and efficacy data from PORTOLA, the first successfully completed, randomized clinical trial in patients with refractory or relapsed AIH. Final data from PORTOLA will be presented as an oral presentation at The Liver Meeting 2025, on November 10th in Washington, DC, by Dr. Craig Lammert, Associate Professor of Medicine at Indiana University School of Medicine and Executive Director for the Autoimmune Hepatitis Association. Kezar submitted a comprehensive report to the FDA that integrated safety, efficacy and pharmacology data across more than 300 patients and healthy volunteers enrolled to zetomipzomib clinical trials, as well as a risk mitigation plan for out-patient monitoring for future trials that was modeled after approved injectable therapeutics. In their written response, the FDA requested that Kezar conduct a stand-alone study to define the pharmacokinetics of zetomipzomib in subjects with significant hepatic impairment prior to the initiation of another clinical trial in AIH. Notably, Kezar informed the FDA that they would exclude AIH patients with significant hepatic impairment in the proposed registration-enabling study. This interim study required by the FDA would delay future trials of zetomipzomib in AIH by approximately 2 years. In addition, the FDA has required future clinical trials of zetomipzomib to include 48-hour patient monitoring in a clinical research unit, which would likely hinder patient enrollment and participation.