Abstract: FR-OR035
Safety and Preliminary Efficacy of Zetomipzomib from the PALIZADE Phase 2b Clinical Trial in Patients with Lupus Nephritis
Session Information
- Glomerular Disease Outcomes: Measuring What Matters
November 07, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Anand, Neel K, Kezar Life Sciences Inc, South San Francisco, California, United States
- Desai, Shraddha, Kezar Life Sciences Inc, South San Francisco, California, United States
- Lowe, Eric, Kezar Life Sciences Inc, South San Francisco, California, United States
- Muchamuel, Tony, Kezar Life Sciences Inc, South San Francisco, California, United States
- Palaniswamy, Kiruthi, Kezar Life Sciences Inc, South San Francisco, California, United States
- Peterson, Rachel, Kezar Life Sciences Inc, South San Francisco, California, United States
- Ray, Kathryn, Kezar Life Sciences Inc, South San Francisco, California, United States
- To, Zung P, Kezar Life Sciences Inc, South San Francisco, California, United States
- Whang, Jennifer, Kezar Life Sciences Inc, South San Francisco, California, United States
- Leff, Richard, Kezar Life Sciences Inc, South San Francisco, California, United States
Background
Zetomipzomib (zeto), a selective immunoproteasome inhibitor, has shown anti-inflammatory activity in patients (pts) with lupus nephritis (LN) in the open-label Phase 2 MISSION study. PALIZADE (NCT05781750), a Phase 2b, randomized (1:1:1), double-blind, controlled study compared weekly subcutaneous administration of zeto (30 mg or 60 mg) to placebo (pbo) in pts with active biopsy-proven LN (Class III/IV ± V or V) on MMF or equivalent plus corticosteroids tapered to ≤5 mg/day over 16 week(W)s. Enrollment and dosing were paused following 4 fatalities (1-pbo, 2-30 mg arm, 1-60 mg arm) and other treatment-emergent serious adverse events (TESAEs) with similar patterns.
Methods
Planned enrollment was 279 pts (249 with Class III/IV ± V and up to 30 with pure Class V) over 52 Ws of treatment with a primary endpoint at W37. At termination, 84 pts were enrolled with mean treatment duration of 16.7 Ws. All pts were included in the safety analysis; 39 pts with proliferative LN reaching W25 were included in the efficacy analysis. Preliminary data included changes in 24-hour urine protein-to-creatine ratio (UPCR) and serologic markers at W25. Biomarker analysis was conducted on whole blood samples.
Results
Pts were mostly female (93%) with mean age of 32.1 years, SLEDAI-2K of 11.2, LN duration of 3.7 years, and baseline UPCR of 3.5 mg/mg. Four fatalities occurred in pts with pre-existing comorbidities (e.g. possible systemic infections) or LN disease co-morbidities (e.g. cardiovascular). The most common TEAEs were injection site reactions (98% Grades 1 or 2) and systemic injection reactions (97% Grades 1 or 2). Among 39 pts with Class III/IV ± V who reached W25, 5/12 (42%) receiving 60 mg zeto achieved UPCR ≤0.5 at W25. Median UPCR reduction was -79% at W25 with zeto 60 mg. Improvements in anti-dsDNA, C3, and C4 were observed across zeto arms.
Conclusion
Safety data indicates a similar profile between zetomipzomib 30 mg and 60 mg arms and aligns with data from the prior MISSION study. Fatalities were associated with possible pre-existing co-morbidities or underlying LN disease characteristics. Preliminary efficacy results indicate encouraging clinical activity in pts with Class III/IV ± V LN receiving 60 mg zeto.
Funding
- Commercial Support – Kezar Life Sciences, Inc