Abstract: PO1913
Treatment of Systemic Lupus Erythematosus with or Without Nephritis with the Immunoproteasome Inhibitor KZR-616: Initial Results of the MISSION Study
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Trials - 3
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Farmer, Mary Katherine, Kezar Life Sciences, Inc, South San Francisco, California, United States
- Parikh, Samir V., The Ohio State University, Columbus, Ohio, United States
- Furie, Richard, Northwell Health, Great Neck, New York, United States
- Kirk, Christopher, Kezar Life Sciences, Inc, South San Francisco, California, United States
- Harvey, Ken, Kezar Life Sciences, Inc, South San Francisco, California, United States
- Bomba, Darrin, Kezar Life Sciences, Inc, South San Francisco, California, United States
Background
Immunoproteasome inhibition demonstrated therapeutic potential in preclinical models of systemic lupus erythematosus (SLE) and lupus nephritis (LN). KZR-616 is a first-in-class selective immunoproteasome inhibitor, which has been safe and well tolerated in early clinical trials. One hundred subjects across 2 healthy volunteer studies, with dosing of KZR-616 up to 75mg SC, achieved target levels of immunoproteasome inhibition at doses ≥30mg. Here we report safety, tolerability and exploratory efficacy data from the Phase 1b portion of MISSION (KZR-616-002; NCT: NCT03393013), a clinical trial in which KZR-616 was administered to patients with active SLE with or without LN.
Methods
In this open-label dose-escalation study, SLE patients (per SLICC classification criteria) with SLEDAI ≥4 despite stable background therapy received KZR-616 at doses of 45mg (Cohort 1), 60mg (Cohort 2), or 60mg following a step-up dose (Cohorts 2a, 2b, 2c) SC weekly through Week 13 (W13) with 12 weeks of follow-up.
Results
To date, 39 patients with SLE, including 2 patients with active proliferative LN, have enrolled in MISSION. The majority of TEAEs have been mild or moderate with injection site reactions the most common TEAE. Tolerability has improved with an initial step-up dosing regime, subsequent doses and the introduction of a lyophilized formulation. To date, no patients have discontinued from cohorts after implementation of these protocol modifications. Multiple measures of disease activity improved from Baseline to W13 and persisted through W25; no patients worsened over 13 weeks. KZR-616 administration resulted in improvements in multiple serologic markers as well as reduced expression of inflammatory gene expression modules. Both patients with biopsy-proven active proliferative LN had reductions in proteinuria.
Conclusion
KZR-616 has been safe and tolerated at a target dose of 60 mg weekly. Step-up dosing, use of select pre-medications, and/or introduction of a lyophilized preparation have increased its tolerability. The administration of KZR-616 resulted in improvement across multiple disease activity measures as well as serologic markers, including improvement in proteinuria in patients with active proliferative LN. MISSION is an on-going study now focused on patients with LN.
Funding
- Commercial Support –