FDA Lifts Hold on Kezar's Liver Drug Trial, Next Stop Lupus Study

The FDA has lifted the partial clinical hold on Kezar Life Sciences' KZR completed PORTOLA Phase 2a trial evaluating zetomipzomib in autoimmune hepatitis. The company plans to respond to the FDA with a request to lift the clinical hold on zetomipzomib in lupus nephritis, as it has met with the Independent Data Monitoring Committee to review the safety profile. Kezar has suspended the development of zetomipzomib in lupus nephritis to focus on AIH, but plans to restart the lupus nephritis trial with FDA approval.

The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on Kezar Life Sciences' completed PORTOLA Phase 2a trial evaluating zetomipzomib for the treatment of patients with autoimmune hepatitis (AIH). The decision follows a comprehensive safety assessment conducted by the FDA's Division of Hepatology and Nutrition.

Chris Kirk, PhD, CEO and co-founder of Kezar Life Sciences, expressed optimism about the FDA's decision, stating, "We are pleased that the FDA has lifted the partial clinical hold on zetomipzomib in AIH after their review of our comprehensive safety assessment of the zetomipzomib program. We continue to believe that zetomipzomib has the potential to positively transform the lives of patients living with AIH" [1].

Kezar Life Sciences has temporarily suspended the development of zetomipzomib in lupus nephritis (LN) to focus on AIH. However, the company has met with the Independent Data Monitoring Committee (IDMC) to review the safety profile of zetomipzomib in the previously terminated PALIZADE clinical trial. Based on this feedback and internal analysis of safety data across all clinical studies involving zetomipzomib, Kezar plans to request the FDA to lift the clinical hold on zetomipzomib in LN [2].

Zetomipzomib is a first-in-class selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research indicates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Clinical trials have shown that zetomipzomib exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases [1].

Autoimmune hepatitis (AIH) is a rare chronic disease in which the immune system attacks the liver, causing inflammation and tissue damage. Lifelong maintenance therapy is required to avoid relapse and burdensome adverse effects. If left untreated, AIH can lead to cirrhosis, liver failure, and hepatocellular carcinoma. In the United States, AIH affects approximately 100,000 individuals, with incidence rates increasing. The cause of this condition remains unclear, with females affected four times as often as males. Standard of care treatment for AIH is chronic, immunosuppressive treatment with corticosteroids that frequently cause life-altering side effects, including diabetes, osteoporotic fractures, and cataracts [1].

Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases. Zetomipzomib is currently being evaluated for autoimmune hepatitis and has the potential to address multiple chronic immune-mediated diseases [1].

References:
[1] https://www.biospace.com/press-releases/kezar-life-sciences-announces-fda-has-lifted-partial-clinical-hold-on-portola-phase-2a-trial-evaluating-zetomipzomib-for-the-treatment-of-patients-with-autoimmune-hepatitis
[2] https://www.morningstar.com/news/business-wire/20250715420439/kezar-life-sciences-announces-fda-has-lifted-partial-clinical-hold-on-portola-phase-2a-trial-evaluating-zetomipzomib-for-the-treatment-of-patients-with-autoimmune-hepatitis