공시 • Nov 15
Kezar Life Sciences, Inc. Presents Positive Complete Results from the Mission Phase 2 Trial Evaluating Zetomipzomib in Lupus Nephritis At the American College of Rheumatology Convergence 2022
Kezar Life Sciences, Inc. announced that it presented the complete data set from the MISSION Phase 2 clinical trial evaluating zetomipzomib in active lupus nephritis (LN) at the American College of Rheumatology (ACR) Convergence 2022 in Philadelphia, PA. 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), Cutaneous Lupus Erythematosus Severity Index-Activity (CLASI-A), 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 steady and clinically meaningful renal responses with additional ORRs and CRRs observed during the safety follow-up period. Overall Renal Responses: 10 out 17 patients (58.8%) achieved an ORR as early as Week 13. 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. In addition, UPCR was reduced to clinically meaningful levels: 11 of 17 patients (64.7%) achieved a UPCR of 0.5 or less at EOS. 15 of 17 patients (88.2%) achieved a UPCR of 0.7 or less at EOS. Median UPCR was 0.32 at EOS. Complete Renal Responses: 5 out 17 patients (29.4%) achieved a CRR as early as Week 13. At EOT, 6 of 17 patients (35.3%) achieved a CRR, a key secondary efficacy endpoint, measured as 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 is associated with active inflammation in the kidney, decreased and showed a strong correlation to UPCR across all timepoints in the study. These data suggest that patients had active inflammation at baseline despite standard-of-care therapy and that the addition of zetomipzomib reduced 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. Key measurements of SLE disease activity were reduced. There was no evidence of early rebound of inflammation following discontinuation of zetomipzomib. SLEDAI-2K, a global assessment of SLE disease activity, reduced from a mean of 11.3 at baseline to 6.5 at EOT and 5.8 at EOS. CLASI-A, a measure of active SLE skin disease, was elevated in 11 patients at baseline, and was reduced from a mean of 5.7 at baseline to 2.6 at EOT and 3.0 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. Biomarkers of SLE activity improved or normalized in patients with abnormal baseline levels. 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, and improvement was maintained in 9 patients at EOS. 4 of 5 patients with abnormally low C3 complement at baseline demonstrated improvement at EOT. 3 of 4 patients with abnormally low C4 complement at baseline demonstrated improvement at EOT. Safety: Zetomipzomib continued to be well-tolerated over the course of the 37-week trial, demonstrating a favorable safety and tolerability profile with no new safety signals during the follow-up period. Overall, adverse events were generally mild-to-moderate (Grade 1 or 2) and were consistent with what was previously reported with topline data from the MISSION Phase 2 clinical trial. Early terminations occurred in 4 out of 21 patients. No opportunistic or Grade 3 infections were reported in the trial.
