The clinical hold doesn’t cover its drug’s Investigational New Drug application for autoimmune hepatitis, for which the Phase IIa PORTOLA trial is ongoing.
Kezar Life Sciences on Friday announced that the FDA has placed a clinical hold on the development program for the investigational immunoproteasome inhibitor zetomipzomib in lupus nephritis.
The regulatory action comes after Kezar announced last week that four patients in the Phase IIb PALIZADE trial died after zetomipzomib treatment. The biotech has yet to release a detailed analysis of the deaths, only revealing at the time that it observed “a common pattern of symptoms and proximity to dosing.”
Kezar also flagged other serious adverse events (SAE) that, while nonfatal, nevertheless “showed a similar proximity to dosing.” The company has since voluntarily suspended enrollment into and dosing in PALIZADE, and has started work on potential risk mitigation strategies for zetomipzomib.
The FDA is expected to issue a formal letter for the clinical hold in the coming weeks.
Kezar CEO Chris Kirk said in a statement that the company is “steadfastly committed to patient safety” and has focused its efforts “to investigating these cases.”
Meanwhile, Kezar will continue to develop zetomipzomib for autoimmune hepatitis, for which its Investigational New Drug is unaffected by the clinical hold, according to Kirk. “Our Phase IIa PORTOLA clinical trial of zetomipzomib in patients with autoimmune hepatitis remains active, and we have not observed any Grade 4 or 5 SAEs in the PORTOLA trial to date.”
Zetomipzomib is an investigational subcutaneous blocker of immunoproteasome proteins, which normally function to maintain a healthy balance in the immune system. Through this mechanism of action, zetomipzomib helps suppress overactive inflammatory pathways, such as the activity of effector cells and the production of cytokines.
In November 2022, Kezar revealed complete data from the Phase II MISSION study of zetomipzomib in lupus nephritis. At 37 weeks, 15 of 17 treated patients achieved at least a 50% reduction in proteinuria from baseline, resulting in an 88.2% overall renal response rate. Data also showed that zetomipzomib suppressed renal inflammation, an effect that lasted up to 12 weeks after stopping treatment.
At the time, Kezar also touted the favorable safety profile of zetomipzomib, with observed side effects being mild or moderate in severity. MISSION did not detect opportunistic or grade 3 infections.
Kezar’s mid-stage safety dilemma comes as its bigger competitors pull ahead in the lupus space. Late last month, Roche announced that its therapeutic antibody Gazyva (obinutuzumab) aced the Phase III REGENCY study, demonstrating “statistically significant and clinically meaningful treatment benefits” in patients with active lupus nephritis. The pharma did not provide specific data from REGENCY.
Just a few days earlier, Biogen and UCB also notched a late-stage victory in lupus, with the investigational dapirolizumab pegol clearing the Phase III PHOENYCS GO study in systemic lupus erythematosus. The partners are gearing up to start another late-stage trial for dapirolizumab pegol this year.
