Data from Aurora clinical programunderscores value of Lupkynis (voclosporin) for patients with lupus nephritis at ACR 2023 meeting

The data reinforce previous findings on the safety and effectiveness of Lupkynis (voclosporin), a second generation calcineurin inhibitor (CNI), for the treatment of adult patients with active lupus nephritis (LN), as shown in the AURORA Clinical Program, comprised of the Phase III AURORA 1 clinical trial and the Phase III AURORA 2 extension study.

An oral presentation demonstrated that initial therapy with Lupkynis plus standard of care reduced proteinuria and patient exposure to toxicities, compared to a conventional regimen consisting of higher doses of both mycophenolate mofetil (MMF) and glucocorticoids alone. Safety and efficacy outcomes for propensity-matched patients with active LN from the Aspreva Lupus Management Study (ALMS) and the AURORA 1 study were assessed at three and six months. In ALMS, MMF was dosed to a target of 3 g/day with oral glucocorticoids initiated at a maximum dose of 60 mg/day and tapered every two weeks to 10 mg/day. In AURORA 1, patients received Lupkynis 23.7 mg BID in combination with MMF (target dose 2 g/day) and oral glucocorticoids (starting dose of 25 mg/day tapered to 2.5 mg/day by Week 16). The data showed an improved safety profile over the first six months of treatment with Lupkynis in combination with low-dose glucocorticoids and lower-dose MMF without compromising efficacy.

“The findings from the propensity analysis of the ALMS and AURORA 1 studies support the use of a triple immunosuppressive regimen containing Lupkynis for the treatment of active LN. Conventional therapeutic regimens for LN have incomplete efficacy and significant toxicities. This study adds to the growing body of data supporting the evolving treatment paradigm for LN,” said lead study author Maria Dall’Era, M.D., Chief and Professor of Medicine in the Division of Rheumatology, University of California, San Francisco.

A post-hoc, pooled analysis of the Phase II AURA-LV and Phase III AURORA 1 studies found that Lupkynis with MMF and low-dose glucocorticoids resulted in earlier and greater reductions in proteinuria in LN patients with proteinuria greater than =2 g/day and greater numeric achievement of complete renal response across biopsy classes, races, and ethnicities. Consistent with results from the overall pooled study population, patients with urine protein creatinine ratio (UPCR) greater than 2 g/g at baseline treated with Lupkynis achieved significantly higher complete renal response rates at one year than patients treated with MMF and low-dose steroids alone, regardless of baseline demographics or clinical characteristics.

“The research presented at ACR this week further supports the importance of a Lupkynis based treatment regimen to help preserve kidney function in LN patients by producing earlier and greater reductions in proteinuria while allowing patients to maintain stable renal function. We are proud of our sustained research in autoimmune diseases like lupus and remain committed to helping improve kidney health for people living with lupus nephritis,” said Dr. Greg Keenan, Chief Medical Officer of Aurinia.

To characterize the long-term renal impact of Lupkynis at the histologic level, researchers analyzed repeat kidney biopsies from a subset of patients in AURORA 2, including 16 patients in the active treatment arm who received Lupkynis in combination with MMF and low-dose glucocorticoids and 10 patients in the control arm treated with MMF and low-dose glucocorticoids alone. Histologic changes from baseline to approximately 18 months post-treatment were assessed. Across both study arms, activity scores, which measured active inflammation in LN, improved to a similar degree, while the chronicity scores, a measure of irreversible kidney injury, remained stable. These results confirmed the safety profile of Lupkynis showing no associated chronic injury with use.

Importantly, patients treated with Lupkynis in the overall AURORA 2 cohort maintained stable renal function over the last two years of the study

In a subset analysis of three years of data from the AURORA Clinical Program, 44.4% of Black patients treated with Lupkynis experienced an improvement in complete renal response at 36 months (n=18) compared to 14.3% of Black patients who achieved complete renal response when treated with MMF and glucocorticoids alone (n= 7 OR: 4.17 (Ci; 0.41, >9.99), p=0.22). These findings among Black patients, a population that often experiences worse outcomes and lower responses to LN treatment, are consistent with the treatment response seen across all racial and ethnic groups treated with Lupkynis in the AURORA Clinical Program. These results were also recently presented at the annual American Society of Nephrology Kidney Week 2023.

Additional data assessed the disposition of cyclosporine (CSA), tacrolimus (TAC), and voclosporin (VCS) in mouse kidneys relative to its systemic drug exposure. The study found differential retention and distribution of the three therapies in mice, consistent with findings from a literature review of their systemic and renal clearance in humans. The assessment of mouse kidneys showed that CSA and TAC had higher drug exposure, while the literature review showed greater than 90% renal reabsorption in humans for CSA and TAC. Comparatively, renal handling of VCS suggested significant tubular secretion. The higher rate of secretion and lower overall renal exposure to VCS may be associated with improved safety when compared to more diffuse distribution and greater renal retention of CSA and TAC.