FDA Lifts Partial Hold on Kezar's Zetomipzomib Trial, Company Considers Reviving Lupus Program

The pharmaceutical landscape saw a significant development as Kezar Life Sciences announced that the U.S. Food and Drug Administration (FDA) has lifted a partial clinical hold on its phase 2a Portola trial. The study is evaluating zetomipzomib, a selective immunoproteasome inhibitor, in patients with autoimmune hepatitis (AIH).

Autoimmune Hepatitis Trial Resumes

Kezar's CEO, Chris Kirk, Ph.D., expressed optimism about the FDA's decision, which came after a "comprehensive safety assessment of the zetomipzomib program." The partial hold, implemented in November 2024, was related to safety concerns for placebo patients transitioning to active treatment in the open-label extension of the study.

Despite the setback, recent topline data from the Portola trial has shown promise, with zetomipzomib demonstrating a 36% rate of complete biochemical response and a "favorable safety profile" in AIH patients. Kirk emphasized the company's belief in zetomipzomib's potential to "positively transform the lives of patients living with AIH."

Potential Revival of Lupus Nephritis Program

While the AIH trial moves forward, a separate clinical hold on zetomipzomib in lupus nephritis (LN) remains in effect. This hold, initiated in October 2024, followed the deaths of four patients in the Philippines and Argentina during the phase 2b Palizade trial.

Initially, Kezar had decided to suspend its lupus work to focus on the AIH indication. However, the company is now reconsidering this decision based on recommendations from Palizade's independent data monitoring committee. Kezar plans to request the FDA's Division of Rheumatology and Transplant Medicine to lift the clinical hold on zetomipzomib in LN, citing internal analysis of safety data across all clinical studies involving the drug.

Looking Ahead

As Kezar prepares to engage with the FDA on the design of the next clinical trial for zetomipzomib in AIH, the biopharmaceutical industry watches closely. The potential resurrection of the lupus nephritis program, if successful, could significantly expand the therapeutic applications of zetomipzomib and impact Kezar's pipeline strategy.

The coming months will be crucial for Kezar as it navigates regulatory discussions and aims to advance its clinical programs, potentially reshaping its approach to autoimmune diseases.