KZR-616, a first-in-class selective immunoproteasome inhibitor, demonstrated a favorable safety and tolerability profile in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN), according to data presented at ACR Convergence 2020.
In the Phase 1b portion of the MISSION study, 41 patients with SLE, including 2 patients with active LN, with SLEDAI ≥4 despite stable background therapy received KZR-616 at doses of 45 mg (Cohort 1), 60 mg (Cohort 2), 60 mg following a step-up dose (Cohorts 2a, 2b, 2c), or 75 mg (Cohort 3) SC weekly through Week 13 (W13) with 12 weeks of follow-up.
The most common treatment emergent adverse event was transient injection-site reaction. Most treatment emergent adverse event were mild or moderate. A dose step-up strategy, use of the lyophilized formulation, subsequent doses, and use of pre-medication improved tolerability. As of the presentation, no patients had discontinued from later cohorts
From baseline to week 13, all measures of disease activity improved and were maintained during the follow-up period.
Improvements in multiple serologic markers of disease activity and reductions in expression of inflammatory gene expression modules were noted.
The 2 patients with active proliferative LN had >50% reductions in urine protein:creatinine ratios (UPCR) from baseline.
Treatment of SLE with or Without Nephritis with the Immunoproteasome Inhibitor KZR-616: Updated Results of the MISSION Study. Presented at: ACR Convergence 2020. Abstract Number: 0855