FDA Places Partial Clinical Hold on Kezar's Autoimmune Hepatitis Trial of Zetomipzomib
核心洞察
The FDA has placed a partial clinical hold on Kezar's PORTOLA Phase IIa study of zetomipzomib in autoimmune hepatitis (搜索) patients, following a previous hold on a lupus nephritis (搜索) trial.
The hold restricts new patients from entering the open-label extension, but allows current participants to continue treatment with adjusted prednisone dosage.
Kezar is investigating safety events from the lupus nephritis (搜索) trial to guide patient management in ongoing and future zetomipzomib studies.
The FDA has placed a partial clinical hold on Kezar Life Sciences' PORTOLA study, a Phase IIa trial evaluating zetomipzomib in patients with autoimmune hepatitis (搜索). This follows a previous clinical hold on the PALIZADE study, which investigated zetomipzomib in lupus nephritis (搜索) patients.
The PORTOLA trial is a placebo-controlled, randomized, double-blind study involving 24 patients with autoimmune hepatitis (搜索). The trial aims to determine if zetomipzomib can help patients achieve a complete biochemical response after 24 weeks. Kezar plans to release topline data in the first half of 2025.
Details of the Clinical Hold
Under the partial clinical hold, the last four patients enrolled in the PORTOLA study can continue in the double-blind portion but cannot proceed to the open-label extension (OLE). Patients currently in the OLE may continue zetomipzomib treatment, but their prednisone dosage cannot be reduced below 5mg/day. Those who have tapered below this level will have their dosage increased back to 5mg/day.
Context of Previous Hold and Trial Adjustments
The PALIZADE trial, which studied zetomipzomib in lupus nephritis (搜索), was previously halted after four patient deaths, including one in the placebo arm. Following this, Kezar discontinued zetomipzomib development for lupus and focused on autoimmune hepatitis (搜索). The company is unblinding the PALIZADE trial and conducting a thorough safety investigation.
Initially, the Independent Data Monitoring Committee (IDMC) recommended that the PORTOLA trial proceed without changes after reviewing safety data from all enrolled patients, including those in the OLE phase.
Company Statement
Kezar's CEO, Dr. Chris Kirk, stated, "We are working to understand the safety events that occurred in the PALIZADE trial in lupus nephritis (搜索), including deaths that occurred in both the placebo and drug arms, so that we can provide patients and physicians appropriate guidance during our ongoing and future clinical trials."
Kezar's Streamlined Focus
In August, Kezar halted the development of its Phase I solid tumor drug KZR-261 to concentrate on zetomipzomib.
About Zetomipzomib
Zetomipzomib is an innovative, selective immunoproteasome inhibitor targeting the LMP7 (搜索) immunoproteasome subunit.