Chicago—More than 500,000 individuals in the United States are affected by systemic lupus erythematosus (SLE), and up to 60% of patients with SLE develop lupus nephritis (LN). Severe LN progresses to end-stage renal disease (ESRD) within 15 years of diagnosis in 10% to 30% of patients. Patients with SLE with renal damage have a 14-fold increased risk of premature death; SLE patients with ESRD have a >60-fold risk of premature death.
There are no US FDA or European Medicines Agency approved therapies for LN; the American College of Rheumatology recommends treatment with intravenous cyclophosphamide (IVC) or mycophenolate mofetil (MMF) as first-line immunosuppressive therapy (standard of care). Achieving clinical remission or renal response predicts long-term outcomes for this patient population.
Voclosporin (VCS), a novel calcineurin inhibitor (CNI), is intended for the treatment of autoimmune diseases such as LN. In the AURA-LV (Aurina Urinary Protein Reduction Active-Lupus Voclosporin) study, researchers sought to evaluate whether VCS added to standard of care increases speed of remission as well as overall remission rates in the presence of extremely low steroids. Samir Parikh, MD, and colleagues reported phase 2b results of AURA-LV during a poster session at the NKF 2017 Spring Clinical Meetings in a poster titled Treatment of Active Lupus Nephritis with Voclosporin: Rapid Remission Over 48 Weeks. Data from the AURA-LV Study.
AURA-LV is a worldwide placebo controlled trial that enrolled 265 patients in 20 countries. Patients received 23.7 mg or 39.5 mg VCS twice a day or placebo. All patients also received background therapy of MMF 2 g per day and low dose steroids. The primary end point of interest was complete remission at 24 weeks. Secondary end points included partial response, time to complete remission or partial response, and week 48 remission rates.
The primary and all secondary end points were met at 24 weeks in the two treatment groups. At week 24, both doses of VCS had statistically significant improvement compared with placebo. For patients who achieved complete response, median time to complete response was 7.3 weeks, compared with 12.1 weeks among patients in the placebo group. At 48 weeks, there was a rapid time to complete response for both doses (P<.001).
VCS at 23.7 mg was well tolerated and demonstrated higher complete remission versus placebo, higher partial response, and faster time to complete response; 23.7 mg is the appropriate dose to advance into Phase 3. The AURA phase 2b results support the advancement of VCR into a phase 3 clinical trial and will serve as one of two registration studies for submission of a New Drug Application to the FDA.
“Aurina plans to initiate a phase 3 clinical trial (AURORA) in 2017. This will be a 52-week double-blind placebo controlled study conducted globally in approximately 320 patients to demonstrate that VCS when added to standard of care can increase overall renal response (remission) rates in the presence of low steroids,” the researchers said.
Source: Parikh SV, Pendergraft WF, Tumlin JA, Saxena R, Solomons N, Huizinga RB. Treatment of active lupus nephritis with voclosporin: rapid remission over 48 weeks. Data form the AURA-LV study. Poster presented at the National Kidney Foundation 2017 Spring Clinical Meetings, April 19-22, 2017, Orlando, Florida.