Slide 1: Renal Biopsy Sub-study April 2023
Renal Biopsy Sub-study April 2023
Slide 2: LUPKYNIS indication and limitations of use
indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN) Limitations of use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in
Slide 3: Renal Biopsy Sub-study Background
Renal Biopsy Sub-study Background • The clinical utility of LUPKYNIS, a novel, second generation CNI, in lupus nephritis has been established1-3 • LUPKYNIS has shown higher rates of remission and response over 3 years in placebo-controlled clinical trials against a background of the then standard of
Slide 4: Nephrotoxicity Associated with First-Generation CNIs
Cumulative incidence of CKD, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2, among 69,321 people who received nonrenal solid organ transplants in the United States between 1990 and 2000. Incidence of chronic kidney disease following nonrenal solid organ transplantation3 Nephro
Slide 5: LUPKYNIS safety considerations versus first-generation CNIs
• Long-term safety data for first-generation CNIs in non-lupus nephritis conditions have created questions regarding safety associated with the long-term use of LUPKYNIS in patients with LN • Several studies suggest LUPKYNIS does not possess many of the clinical safety considerations associated with
Slide 6: Characteristic Histopathology Associated with CNI-Nephrotoxicity
Characteristic Histopathology Associated with CNI-Nephrotoxicity Histopathologic associations emerged from patients receiving solid-organ transplants with sequential biopsies. These were not controlled with patients who did not receive CNI therapy. 1. Hardinger K. Cyclosporine and tacrolimus nephrot
Slide 7: AURORA Biopsy Sub-Study
AURORA Biopsy Sub-Study • AURORA 1 is the 357 patient, Phase 3, one-year, lupus nephritis study comparing LUPKYNIS to placebo, in combination with the then SOC • AURORA 2 is the Phase 3, global, double-blind, two-year continuation study of AURORA 1; 216 patients enrolled into AURORA 2, providing LUP
Slide 8: LUPKYNIS Renal Biopsy Sub-Study Methods
LUPKYNIS Renal Biopsy Sub-Study Methods • Twenty-six patients agreed to participate in the biopsy sub-study • 10 patients were in the standard of care treatment group • 16 patients were in the LUPKYNIS treatment group • After approximately 18-months of treatment, participating patients underwent a f
Slide 9: Biopsy Sub-study Patient Demographics Similar to the Main AURORA 1 Study
Biopsy Sub-study Patient Demographics Similar to the Main AURORA 1 Study SOC n=10 LUPKYNIS n=16 AURORA 1 N=357 Age, years Mean (SD) 36.2 (12.1) 29.8 (8.6) 33.2 (10.96) Sex, n (%) Female 9 (90) 15 (93.8) 313 (87.7) Race, n (%) White 3 (30) 5 (31.3) 129 (36.1) Asian 3 (30) 3 (18.8) 109 (30.5) Other* 4
Slide 10: LUPKYNIS Biopsy Study - NIH Scoring system
Activity Indices Score Endocapillary hypercellularity 0-3 Neutrophils / karyorrhexis 0-3 Hyaline deposits / wire loops 0-3 Fibrinoid necrosis (0-3) x 2 Cellular or fibrocellular crescents (0-3) x2 Interstitial inflammation (0-3) x2 Total Score 0-24 Chronicity Indices Global glomerulosclerosis 0-3 Fi
Slide 11: Biopsy Sub-study Histology Results
Biopsy Sub-study Histology Results Overall, activity scores decreased, and chronicity scores were stable Data from pretreatment baseline in AURORA 1 (i.e., BL) and after 15-18 months of study treatment (i.e., Follow-up) for 16 patients in the voclosporin group and 10 patients in the standard of care
Slide 12: Conclusions
Conclusions • Long-term use of first-generation CNIs such as cyclosporine and tacrolimus are associated with a variety of acute findings including renal dysfunction, glucose dysregulation, hyperkalemia, hypomagnesemia, drug-drug interactions with MMF, and serum lipid elevation • Irreversible renal d
Slide 13: Conclusions Continued
Conclusions Continued: • The biopsy sub-study of a representative population demonstrated results consistent with the established clinical safety and efficacy of LUPKYNIS, a novel, second-generation CNI • NIH disease activity scores, a histological measure of kidney inflammation, decreased substanti
Slide 14: Renal Biopsy Sub-study April 2023
Renal Biopsy Sub-study April 2023