AURA: Voclosporin Gives Hope to Patients With Lupus Nephritis

Issue: December 2016

WASHINGTON — A large proportion of patients with lupus nephritis who were treated with a low dose of voclosporin met the primary endpoint of complete remission, according to results of the AURA study presented here at the American College of Rheumatology Annual Meeting.

“We face a crisis in the treatment of lupus nephritis at this time,” Mary Anne Dooley, MD, of Dooley Rheumatology, Chapel Hill Doctors, in Chapel Hill, N.C. “More than 40% of patients are non-responders at 6 months.”

She added the pharmacokinetic and pharmacodynamic profile of voclosporin is stable.

Dooley and colleagues enrolled 265 patients with active lupus nephritis to be treated with voclosporin (Aurinia Pharmaceuticals). There were two voclosporin treatment groups: 23.7 mg twice a day, which they described as the low-dose group (n = 89), and 39.5 mg twice a day, which was defined as the high-dose group (n = 88). The study also included a control arm assigned placebo (n =88). Patients were also treated with mycophenolate mofetil 2 g per day and steroids.

Complete remission, which was defined as a urine protein/creatinine ratio of less than or equal to 0.5 mg/mg using first morning void with an estimated glomerular filtration rate greater than or equal to 60 mL/min without a decrease of greater than or equal to 20%, was the primary endpoint. Time to complete remission, partial remission (defined as a 50% reduction in proteinuria) and time to partial remission were the other endpoints the researchers analyzed.

Results indicated the low dose of the drug yielded a 32.6% complete response rate, compared with 27.3% for the high dose (P = .045). The comparison for the treatment arms was also favorable to the low dose compared with the high dose in terms of complete remission (OR = 2.03; P = .045). The complete response rate was 19.3% among controls.

Secondary endpoint results showed a decrease in proteinuria was significantly better in the low-dose arm compared with placebo (P = .047). Partial remission was reported in 70% of patients in the low-dose arm, 49% of those in the high-dose arm and 66% of controls. Time to complete remission was significantly better in the low-dose arm vs. the high-dose arm (P = .002) and in the low-dose arm vs. controls (P = .003).

“Both treatment arms showed a rapid response to therapy that continued to rise through week 6,” Dooley said. “It plateaus between 16 [weeks] and 24 weeks.”

Complete remission was maintained for 7 weeks in the low-dose group, compared to longer than 10 weeks in the high-dose and control groups. Adverse event rates were frequent and comparable across the study arms.

“Almost all patients in the study had an adverse event,” Dooley said, noting a cross-section of infections, infestations and gastrointestinal disorders, among others. “In general, patients’ renal function did decrease but not significantly with voclosporin.”

Thirteen patients have died to date, for an overall mortality rate of 4.9%, according to Dooley.

“The most concerning side effect has been mortality,” she said.

Baseline data showed most patients had early onset disease, with most patient having lupus nephritis for less than 4 years. Eligibility criteria included renal biopsy within 6 months or serologic evidence of active disease. The current data set includes 24-week results. Baseline data showed that the two treatment groups were balanced.

“This is the first global lupus nephritis trial to meet its primary endpoints and all secondary endpoints,” she said. “These promising data will be used to plan subsequent studies of voclosporin in lupus nephritis.” – by Rob Volansky

Reference:

Dooley MA, et al. Abstract #5L. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.

Disclosure: Dooley reports she has associations with Aurinia Pharmaceuticals.