A post-hoc analysis of the Phase 3 AURORA 1 study has demonstrated that lupus nephritis (LN) patients treated with LUPKYNIS® (voclosporin)-based triple immunosuppressive therapy achieved significantly lower proteinuria targets compared to standard therapy. The findings were presented at LUPUS 2025, the 16th International Congress on SLE, held May 21-24 in Toronto, Canada.
The analysis evaluated 357 patients from the AURORA 1 trial, comparing those who received triple therapy (LUPKYNIS, mycophenolate mofetil, and low-dose glucocorticoids) against those who received standard therapy (mycophenolate mofetil and low-dose glucocorticoids alone). Results showed that 60.9% of patients in the triple therapy group (N=109) achieved a urine protein creatinine ratio (UPCR) of ≤0.4 g/g at least once during the 52-week study, compared to only 37.1% in the control group (N=66).
"It is widely known that no level of proteinuria is safe for nephrons and that early reductions in proteinuria are predictive of better long-term kidney outcomes. Yet, UPCR endpoints have varied widely across clinical trials and in clinical practice," said lead study author Maria Dall'Era, M.D., Professor of Medicine in the Division of Rheumatology, University of California, San Francisco.
Dr. Dall'Era added, "This analysis shows that achieving UPCR targets of ≤0.4 g/g may be a feasible goal and that a voclosporin-based triple immunosuppressive therapy regimen can reduce proteinuria to profoundly low levels in a proportion of patients."
Deep Proteinuria Reduction Across Multiple Targets
The study assessed achievement of multiple UPCR targets, including ≤0.4 g/g, ≤0.3 g/g, ≤0.2 g/g (classified as ultra-low UPCR), and ≤0.1 g/g. Patients in the LUPKYNIS-based triple therapy group consistently achieved higher rates across all proteinuria targets compared to the control group. Importantly, adverse event rates remained comparable between both treatment arms.
Dr. Greg Keenan, Chief Medical Officer of Aurinia Pharmaceuticals, emphasized the significance of these findings: "The data presented at LUPUS 2025 highlight the critical role of LUPKYNIS in improving health outcomes for LN patients. Early reduction of proteinuria to the lowest possible levels and long-term preservation of kidney health are key goals of LN therapy."
Lipidomic Profile Improvements
A separate post-hoc analysis from the AURORA 1 study evaluated lipidomic profiles in LN patients based on achievement of proteinuria reductions, including ultra-low UPCR, at Week 52. The analysis revealed a distinct lipidomic profile in patients who achieved ultra-low UPCR.
This builds upon previous findings from AURORA 1 showing that patients who received LUPKYNIS-based triple therapy achieved significantly greater improvements in total and low-density lipoprotein (LDL) cholesterol compared to those in the control group. While researchers note that further investigation is needed to clarify the role of certain lipids in LN patients, these preliminary findings suggest that attaining ultra-low UPCR targets may provide additional benefits beyond kidney protection, potentially contributing to modification of cardiovascular disease risk.
Real-World Data from ENLIGHT-LN Registry
The conference also featured an analysis of real-world baseline data from ENLIGHT-LN, a U.S.-based prospective, observational registry of adult LN patients treated with LUPKYNIS. This registry will provide valuable insights into the real-world effectiveness and safety profile of LUPKYNIS in clinical practice.
About LUPKYNIS and Lupus Nephritis
LUPKYNIS is a second-generation calcineurin inhibitor with a dual mechanism of action. It acts as an immunosuppressant through inhibition of T-cell activation and cytokine production while also promoting podocyte stability in the kidney. The drug received FDA approval in January 2021 as the first oral therapy specifically dedicated to treating adult patients with active lupus nephritis.
Lupus nephritis is a serious kidney inflammation that occurs in approximately 40% of patients with systemic lupus erythematosus (SLE). If left untreated or inadequately controlled, LN can lead to permanent kidney damage, kidney failure, and increased mortality.
The AURORA Clinical Program, which includes the AURORA 1 pivotal trial and AURORA 2 extension trial, demonstrated the importance of triple immunosuppressive therapy with LUPKYNIS, mycophenolate mofetil, and low-dose glucocorticoids to preserve kidney health in lupus nephritis patients without reliance on chronic high-dose glucocorticoids. It is the only clinical program in lupus nephritis to include three years of triple immunosuppressive therapy data.
Future Implications
These findings have significant implications for clinical practice in lupus nephritis management. By demonstrating that deeper reductions in proteinuria are achievable with LUPKYNIS-based triple therapy, clinicians may consider more aggressive treatment approaches to preserve long-term kidney function.
Dr. Keenan concluded, "These data provide compelling evidence that LUPKYNIS-based therapy can achieve significantly lower UPCR targets, potentially reducing the risk of significant kidney damage and other comorbidities."
Aurinia Pharmaceuticals continues to advance research in lupus nephritis, including the development of AUR200, a potential best-in-class therapy for autoimmune diseases that targets both BAFF (B-cell Activating Factor) and APRIL (A Proliferation-Inducing Ligand).
