Kidney Week

Abstract: TH-PO487

Zetomipzomib (KZR-616), a First-in-Class Selective Immunoproteasome Inhibitor for the Treatment of Lupus Nephritis: Preliminary Results From the Phase 2 MISSION Study

Session Information

• Glomerular Diseases: Clinical, Outcomes, Trials - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

• Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Samir V. Parikh,

• Furie, Richard, Northwell Health, New Hyde Park, New York, United States

Richard Furie,

• Saxena, Amit, NYU Langone Health, New York, New York, United States

Amit Saxena,

• Leff, Richard, Kezar Life Sciences Inc, South San Francisco, California, United States

Richard Leff,

• Hua, Steven Y., Kezar Life Sciences Inc, South San Francisco, California, United States

Steven Y. Hua,

• Long, Li, Kezar Life Sciences Inc, South San Francisco, California, United States

Li Long,

• Henig, Noreen Roth, Kezar Life Sciences Inc, South San Francisco, California, United States

Noreen Roth Henig,

Background

The MISSION study (NCT03393013), a Phase 1b/2, open-label study is to evaluate safety, tolerability, and exploratory efficacy of zetomipzomib in patients with systemic lupus erythematosus (SLE) +/- lupus nephritis (LN). In the completed Phase 1b portion, zetomipzomib was safe and well-tolerated and resulted in improvement across disease activity measures as well as biomarkers. The Phase 2 fully enrolled in Nov 2021, and here we present preliminary results from this signal-seeking study.

Methods

MISSION Phase 2 evaluated zetomipzomib at 60 mg subcutaneously (SC) once weekly (QW) for 24 weeks (1^st dose: 30 mg) in patients with active LN (Class III or IV ± Class V) with urine protein to creatinine ratios (UPCR) ≥1 despite background therapy. Safety, tolerability, UPCR, renal function, SLE disease activity, and biomarkers were measured. Interim analysis of laboratory data was performed.

Results

As of October 1, 2021, 5 patients reached end of treatment (Week [W] 25), and 10 patients reached W13; 80% female; mean age 39.4 years; median LN duration 7.6 years; mean UPCR 2.2 (assessed from 24-hour collections); mean eGFR 78.5 mL/min/1.73 m²; all patients were on prednisone, and 8 and 5 patients were on mycophenolate mofetil or mycophenolic acid and hydroxychloroquine, respectively. At end of treatment, 3 of 5 patients achieved a ≥50% reduction in UPCR; 4 of the 5 patients had renal responses (2 complete renal response and 2 partial renal response). Zetomipzomib administration improved UPCR and key biomarkers (eg, anti-dsDNA) as early as W13, and was associated with a favorable safety/tolerability profile. The most common adverse event (AE) was injection site reaction. Most AEs were mild to moderate (Grade ≤2). Two Serious AEs were reported in 2 patients (1 related and 1 unrelated). There were no discontinuations due to drug-related AEs. No opportunistic infections were reported.

Conclusion

Zetomipzomib 60 mg SC QW demonstrated a favorable safety and tolerability profile in patients with active LN who were on stable background therapy in MISSION Phase 2. Zetomipzomib led to clinically meaningful reductions in proteinuria and improvement in key SLE biomarkers. An updated analysis of the completed Phase 2 MISSION study will be shared.

Funding

• Commercial Support –