ORLANDO, Fla.—Voclosporin (VCS), a novel calcineurin inhibitor, is significantly more effective than placebo at achieving rapid complete and partial remission of active lupus nephritis, according to 48-week phase 2b study data.
The AURA-LV (Aurinia Urinary Protein Reduction Active-Lupus With Voclosporin) study compared a low and high dose of VCS (23.7 mg twice daily and 39.5 mg twice daily, respectively) with placebo in 265 patients (89 and 88 in the low- and high-dose VCS groups, respectively, and 88 in the placebo arm). To be included in the study, patients need to be diagnosed with systematic lupus erythematosus based on American College of Rheumatology (ACR) criteria and have biopsy-proven lupus nephritis.
At 48 weeks, complete remission was achieved in about 50% and 40% of the low- and high-dose VCS groups, respectively, compared with about 25% in the placebo group, Samir Parikh, MD, of Ohio State University Medical Center in Columbus, and colleagues reported in a poster presentation. Among patients who achieved a complete response, the median time to complete response was 7.3 weeks for the low-dose VCS group compared with 12.1 weeks for the placebo group. Partial response rates at 48 weeks were similar for both VCS doses (approximately 70%) compared with about 50% in the placebo arm.
“VCS data to date shows a significant improvement over the currently accepted standard of care and does so with low steroid exposure,” Dr Parikh’s group stated.
“The response rates are the highest of any global clinical trial in active lupus nephritis, with 50% complete response at 48 weeks,” Dr Parikh told Renal & Urology News. “Additionally, the patients who attained an early complete response at 24 weeks sustained that response at 48 weeks.”
More than 92% of patients experienced at least 1 adverse event (AEs). AEs more frequently occurred in the VCS groups and were characteristic of immunosuppression and highly active lupus nephritis, according to the investigators.
Dr Parikh and his colleagues concluded that the 23.7 mg twice daily dose of voclosporin is the appropriate dose to advance to a phase 3 trials.
Although no FDA-approved therapies for lupus nephritis exist, ACR recommends intravenous cyclophosphamide or mycophenolate mofetil be used for first-line immunosuppressive therapy for lupus nephritis, the investigators noted. Even with these treatments, most lupus nephritis patients fail to achieve complete remission at 24 weeks.
With the current treatments, remission rates are “really suboptimal,” with complete remission rates of around 15%-20% at 6 months and partial remission rates of 40%-50% at 6 months, Dr Parikh said.
“The thing about volcosporin that makes it a little bit different than the existing calcineurin inhibitors is that it has a modified profile … that allows it to have more stable dosing. You actually get a peak concentration in 2 hours and flat dosing, so you don’t have to measure troughs plus you get more potent calcineurin inhibition.”
As with other calcineurin inhibitors, VCS inhibits the T-cell mediated immune response, which plays an important role in lupus nephritis pathogenesis, Dr Parikh said.
See more coverage from the National Kidney Foundation Spring Clinical meeting.
Parikh SV, Pendergraft WF, Tumlin JA, et al. Treatment of active lupus nephritis with voclosporin: Rapid remission over 48 weeks. Data from the AURA-LV study. Poster presented at the National Kidney Foundation’s 2017 Spring Clinical Meetings in Orlando, Florida, April 18-22). Poster 381.