Additional Relevant Details
Data from a total of 534 patients from AURA-LV and AURORA was integrated and presented, demonstrating that 268 patients with LN treated with voclosporin in combination with mycophenolate mofetil (MMF) and low-dose steroids achieved statistically superior and faster Renal Response rates compared to 266 patients treated with MMF and steroids alone. The effects were also observed in Hispanic patients, a high-risk lupus nephritis population. Treatment with voclosporin resulted in clinically meaningful and a statistically significant higher Renal Response rate of 43.7% compared to 23.3% in the control arm at one year (OR 2.76, 95% CI: 1.88, 4.05; p < 0.0001) and at six months (voclosporin 31.7%; placebo 20.3%), [OR: 2.01; 95% CI: 1.34, 3.01; p=0.0008].The Company also presented PK data analyzed from the AURA-LV and AURORA studies further supporting the potential to eliminate the need for therapeutic drug monitoring. The influence of various covariates on voclosporin’s PK was evaluated based on a population PK model and calcineurin inhibition was estimated using concentration data in the LN population and previously measured inhibition. At the recommended therapeutic dose of 23.7 mg twice daily, sex, body weight, race, age, serum albumin, total bilirubin and estimated glomerular filtration rate (eGFR) demonstrated no clinically relevant effect on voclosporin’s PK parameters. Voclosporin was shown to inhibit calcineurin in a dose-dependent manner. In a quartile exposure analysis, no relationship with the odds ratio for renal response was observed and favored voclosporin in all quartiles. The linear PK profile of voclosporin allows the use of a pharmacodynamic approach instead of a pharmacokinetic approach, in which the dose of voclosporin is adjusted in response to decreases in eGFR.The AURA-LV and AURORA studies were of similar design and conducted in comparable patient populations. The data from both studies for subjects treated with the recommended voclosporin dose of 23.7 mg twice daily (AURORA; n=179, AURA-LV; n=89) or with matching placebo (AURORA; n= 178, AURA-LV; n=88) were therefore pooled for an integrated analysis.