Kezar Life Sciences, Inc. announced that it presented the complete data set from the MISSION Phase 2 clinical trial evaluating zetomipzomib, a novel, first-in-class, selective immunoproteasome inhibitor, in active lupus nephritis (LN) at the American Society of Nephrology's (ASN) Kidney Week 2022 Annual Meeting in Orlando, FL. The MISSION Phase 2 clinical trial was an open-label study designed to demonstrate the responder rate of zetomipzomib in patients with active LN. During the 24-week treatment period, patients received 60 mg of zetomipzomib subcutaneously once weekly (first dose of 30 mg) in addition to stable background therapy.

End-of-treatment (EOT) assessments occurred at Week 25, with completion of the study at Week 37 (EOS). Patients in the MISSION Phase 2 clinical trial received zetomipzomib without induction therapy, which represents a significant difference from other recently published clinical trials in LN. The primary efficacy endpoint for this trial was the proportion of patients achieving an overall renal response (ORR), measured as a 50% or greater reduction in urine protein to creatinine ratio (UPCR) at EOT.

A key secondary efficacy endpoint was the number of patients with a complete renal response (CRR), measured as an absolute reduction in proteinuria values to a UPCR of 0.5 or less, with preserved renal function (eGFR), and corticosteroid use of 10 mg or less prednisone/prednisone equivalent and no use of prohibited medication. Exploratory endpoints included measures of systemic lupus erythematosus (SLE) disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), Physician Global Assessment and Patient Global Assessment scores. Summary of Results from the Completed MISSION Trial: In the MISSION Phase 2 clinical trial, 17 of 21 enrolled patients reached end-of-treatment at Week 25 and end-of-study at Week 37.

Zetomipzomib treatment demonstrated clinically meaningful renal responses with additional ORRs and CRRs observed during the safety follow-up period. Overall Renal Responses: At EOT, 11 of 17 patients (64.7%) achieved an ORR measured as a 50% or greater reduction in UPCR compared to baseline, the primary endpoint of the clinical trial; During the safety follow-up period, clinical responses deepened, and ORRs increased to 16 of 17 patients (94.1%) at Week 29 and 15 of 17 patients (88.2%) at EOS; 12 of 17 patients (70.6%) also reached UPCR of 0.7 or less at EOS. Complete Renal Responses: At EOT, 6 of 17 patients (35.3%) achieved a CRR, including a UPCR of 0.5 or less, stable eGFR, daily prednisone/prednisone equivalent dose of 10 mg or less, and no use of prohibited medication; During the safety follow-up period, an additional patient achieved a CRR, with the total CRRs increasing to 7 of 17 patients (41.2%) at Week 29 and EOS, demonstrating a deepening renal response throughout the 37-week trial.

Urinary CD163, a biomarker that suggests active inflammation in the kidney, showed a strong correlation to UPCR across all timepoints in the study. These data indicate that patients had active inflammation at baseline despite standard-of-care therapy and that the addition of zetomipzomib has the potential to resolve inflammation. By Week 13, 14 of 17 patients (82.4%) achieved a daily corticosteroid dose of 10 mg or less, despite no protocol-mandated steroid taper.

Doses of background immunosuppressive agents remained stable throughout the study, including during the 12-week safety follow-up. Mean eGFR (estimated glomerular filtration rate) remained stable from baseline to EOS. Key measurements of SLE disease activity were reduced and key biomarkers of SLE improved.

There was no evidence of early rebound of inflammation following discontinuation of zetomipzomib: SLEDAI-2K scores reduced from a mean of 11.3 at baseline to 6.5 at EOT and 5.8 at EOS; Physician Global Assessment scores reduced from a mean of 57.2 at baseline to 23.9 at EOT and 16.2 at EOS; Patient Global Assessment scores reduced from a mean of 23.6 at baseline to 10.7 at EOT and 6.6 at EOS; Of the 12 patients with abnormal levels of double-stranded DNA antibody levels (anti-dsDNA) at baseline, 10 patients showed improved or normalized levels of anti-dsDNA at EOT, which improvement was maintained in 9 patients at EOS. Safety: Zetomipzomib continued to be well-tolerated over the course of the 37-week study, demonstrating a favorable safety and tolerability profile. Overall, adverse events were generally mild-to-moderate (Grade 1 or 2) and were consistent with what was previously reported with topline data.

Early terminations occurred in 4 out of 21 patients. No opportunistic or Grade 3 infections were reported in the trial.