The FDA has lifted one of the two clinical holds placed on Kezar Life Sciences’ zetomipzomib, leading the biotech to speculate on whether to reignite another program for the same drug that remains under hold.
The company announced Wednesday that the FDA has lifted the partial hold on Kezar’s phase 2a Portola trial evaluating the selective immunoproteasome inhibitor in autoimmune hepatitis. When the hold was implemented in November 2024, analysts explained that it was related to “potential concerns of some placebo patients among the four patients yet to roll over in the [open-label extension], who could be subject to safety risk upon initiating zetomipzomib treatment.”
Since then, a topline readout from the trial has tied zetomipzomib to a 36% rate of complete biochemical response and a “favorable safety profile.”
Kezar’s CEO, Chris Kirk, Ph.D., explained in this morning’s release that the FDA has now lifted the hold 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,” Kirk added. “We look forward to engaging with the FDA to align on the design of the next clinical trial of zetomipzomib in AIH.”
A separate hold on zetomipzomib in lupus nephritis remains in place. That hold was instigated in October 2024 after a review of emerging safety data revealed the death of four patients in the Philippines and Argentina during the phase 2b Palizade trial.
Kezar has since decided to suspend its lupus work to focus on zetomipzomib in AIH, but today’s release suggests that the company may be having second thoughts after receiving recommendations from Palizade’s independent data monitoring committee for conducting fresh trials in lupus nephritis.
“Based on this feedback and internal analysis of safety data across all clinical studies involving zetomipzomib, Kezar plans to respond to the FDA Division of Rheumatology and Transplant Medicine with a request to lift the clinical hold on zetomipzomib in LN,” the company explained.