FDA Lifts Partial Hold on Kezar's Zetomipzomib Trial for Autoimmune Hepatitis

The U.S. Food and Drug Administration (FDA) has lifted a partial clinical hold on Kezar Life Sciences' phase 2a Portola trial, evaluating the selective immunoproteasome inhibitor zetomipzomib in patients with autoimmune hepatitis (AIH). This development marks a significant step forward for Kezar's AIH program and potentially opens the door for further clinical advancements.

Autoimmune Hepatitis Trial Resumes

The partial hold, implemented in November 2024, was related to safety concerns for placebo patients transitioning to zetomipzomib treatment in the open-label extension of the study. Kezar's CEO, Chris Kirk, Ph.D., stated that the hold was lifted following "their review of our comprehensive safety assessment of the zetomipzomib program."

Prior to the hold, topline results from the Portola trial showed promise, with zetomipzomib demonstrating a 36% rate of complete biochemical response and a "favorable safety profile" in AIH patients. Kirk expressed optimism about the drug's potential, saying, "We continue to believe that zetomipzomib has the potential to positively transform the lives of patients living with AIH."

Lupus Nephritis Program: A Possible Resurrection?

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

Despite initially suspending its lupus work to focus on AIH, Kezar is now considering reviving the LN program. The company has received recommendations from Palizade's independent data monitoring committee for conducting new trials in lupus nephritis. Based on this feedback and internal analysis of safety data across all zetomipzomib clinical studies, Kezar plans to request that the FDA lift the clinical hold on the LN program.

Next Steps and Regulatory Engagement

With the partial hold lifted on the AIH trial, Kezar is preparing to engage with the FDA to align on the design of the next clinical trial for zetomipzomib in AIH. Simultaneously, the company is preparing a response to the FDA's Division of Rheumatology and Transplant Medicine regarding the LN program.

As Kezar navigates these regulatory challenges, the pharmaceutical industry will be watching closely to see how the company balances its AIH and potential LN programs, and whether zetomipzomib can overcome its recent setbacks to deliver on its promise for patients with autoimmune conditions.