麻豆传媒

The high potency calcineurin inhibitor voclosporin plus standard of care was superior to standard of care alone in a phase III study of lupus nephritis known as AURORA.

Renal response at week 52, the primary endpoint, was seen in 40.8% of patients receiving voclosporin plus mycophenolate mofetil (CellCept) and a rapid steroid taper compared with 22.5% of those given mycophenolate and tapered steroids alone, for an odds ratio of 2.65 (95% CI 1.64-4.27, P<0.001), reported Cristina Arriens, MD, of the Oklahoma Medical Research Foundation in Oklahoma City.

"Voclosporin was created by making a small structural change to cyclosporine, incorporating a single carbon extension with a double bond," she explained during her presentation at the . "This resulted in a predictable dose response, potentially eliminating the need for blood level monitoring."

In renal disease, voclosporin reduces T-cell activation and stabilizes podocytes, which protects against proteinuria. It has previously been evaluated in a phase IIb trial known as .

In the current phase III study, the 357 recruited patients had biopsy proven nephritis requiring 1.5 g of proteinuria in proliferative nephritis and 2 g for membranous nephritis. Of these patients, 88% were women, mean age was 31, and one-third were Hispanic.

Renal response, similar to the clinical response endpoint used in previous studies of lupus nephritis, required proteinuria of 0.5 g or less and maintained renal function, but also required that patients be given 10 mg or less/day of prednisone in the final 8 weeks.

Patients randomized to the voclosporin arm were given the oral drug in dosages of 23.7 mg twice per day plus mycophenolate, 2 g/day, with oral steroids, while the control group received placebo plus 2 g/day of mycophenolate and oral steroids. The prednisone dose was required to be rapidly tapered from 25 mg/day to 2.5 mg/day by week 16.

Voclosporin also resulted in greater improvements in various secondary endpoints. Renal response at 24 weeks was seen in 32.4% of the voclosporin group compared with 19.7% of the control group (OR 2.23, 95% CI 1.34-3.72, P=0.002), and partial renal response at week 24 in 70.4% versus 50% (OR 2.43, 95% CI 1.56-3.79, P<0.001). Partial renal response at 52 weeks was achieved by 69.8% of the voclosporin group compared with 51.7% of the control group (OR 2.26, 95% CI 1.45-3.51, P<0.001).

In addition, the median time until the urine protein:creatinine ratio was at or below 0.5 mg/mg was approximately 24 weeks in the voclosporin group versus 53 weeks in the control group.

"Hispanic patients with lupus commonly have more severe and treatment-refractory nephritis," Arriens said. Yet in this study, renal responses among Hispanic patients were seen in 38.6% of the voclosporin group at week 52 compared with 18.6% of controls, for an odds ratio of 3.45. High rates of renal response were also seen among Asian patients in the voclosporin group (41.5% vs 17.9%, P=0.005) and black patients (46.2% vs 15.8%, P=0.045).

The safety profile was similar in the two arms of the trial, with serious adverse events being reported in 20.8% of the voclosporin group and 21.3% of the control group. Serious infections were seen in 10.1% of the voclosporin group and 11.2% of controls. There was one death in the voclosporin group and five in the control group.

In the voclosporin group, there also were no significant decreases in estimated glomerular filtration rate or increases in blood pressure, lipids, or glucose at week 52.