Aurinia Pharmaceuticals recently announced positive top-line results from the voclosporin Phase 2b clinical trial AURA-LV (AURA) in patients with active lupus nephritis (LN) after achieving its primary endpoint.
Voclosporin is an investigational immunosuppressant with a synergistic and dual mechanism of action that can potentially improve near- and long-term outcomes in LN when added to standard of care.
The AURA-LV trial compared voclosporin’s effectiveness in addition to standard of care of mycophenolate mofetil (MMF) against standard of care plus placebo, to achieve complete remission in people with active LN.
The study enrolled 265 participants at centers in more than 20 countries worldwide. Patients had to prove they were diagnosed with LN according to specific criteria.
Participants were then randomized in two dosage groups: one received 23.7 mg or 39.5 mg of voclosporin two times a day, and a second received placebo. All patients received MMF and oral corticosteroids as background therapy.
The patients started with an initial steroids dosage of 500-1000 mg and were then started on 20-25 mg/daily – which was lowered to a dose of 5 mg daily by week 8 and 2.5 mg daily by week 16.
The study met its primary endpoint of measuring the number of patients who achieved complete remission at 24 weeks and confirmed at 26 weeks.
Secondary endpoints included durability of remission, complete remission per the primary analysis at 48 weeks and extra-renal lupus activity to be reported in the future.
“We are very pleased by these encouraging results and are grateful to those that participated in our clinical trials,” Dr. Neil Solomons, Aurinia’s chief medical officer, said in a press release. “The AURA study was conducted under rigorous and stringent criteria, enhancing our confidence in voclosporin’s potential ability to provide a substantial improvement over the currently accepted standard of care, especially given that study participants had such active disease and were exposed to such a low corticosteroid load.”
Regarding the study’s efficacy evaluation, complete remission was met for the low-dose voclosporin group: 32.6% of patients versus 27.3% on high dose and 19.3% in the control arm achieved complete remission. Additionally, the odds ratio indicated that patients were two times more likely to achieve complete remission at 24 weeks.
The primary endpoint was verified using the 24-hour urine data in place of first morning void (FMV) collections, confirming the previous finding of complete remission at 24 weeks.
The secondary endpoint of partial response was met for both voclosporin groups with 69.7% and 65.9% of patients in the low dose and high dose groups, respectively. In contrast, only 49.4% of patients in the control arm achieved PR.
Regarding the study’s safety evaluation, the overall rate of side effects were similar across all groups, but the rate of serious adverse effects (SAEs) were higher in both voclosporin sub-groups – although the nature of the SAEs was consistent with highly active LN.
Aurinia hopes to meet with the U.S. Food and Drug Administration (FDA) later this year to discuss the drug’s further plans for clinical development and plan a path for registration in LN. Aurinia will conduct further analyses of the data, to be released later in 2016. The company is planning to submit the results for presentation at a major medical meeting after the study completes its 48 weeks.
“These preliminary results show great promise and could potentially change the current treatment paradigm for LN,” said Dr. Mary Anne Dooley, LN expert, rheumatologist and chief investigator of the study said. “The remission rates show a meaningful improvement over the current standard of care. Achieving this result given the taper to low dose steroids represents a significant advance. Given the side effects of corticosteroids, limiting the dose could substantially enhance a patient’s quality of life.”