Adding the experimental oral therapy voclosporin to standard treatment is safe, and its use more than doubles complete kidney responses in people with lupus nephritis, results from the Phase 3 AURORA study show.
Aurinia Pharmaceuticals, the company developing voclosporin, plans to finish its rolling application to the U.S. Food and Drug Administration by mid-year, seeking regulatory approval possibly in 2021.
Keisha Gibson, with the University of North Carolina School of Medicine, presented the study, “AURORA Phase 3 Trial Demonstrates Voclosporin Statistical Superiority Over Standard of Care in Lupus Nephritis (LN)” at the ongoing National Kidney Foundation 2020 Spring Clinical Meetings.
Due to the COVID-19 outbreak, the meeting is being broadcast live online.
Voclosporin works by blocking the activity of calcineurin, an enzyme involved in the activation of immune T-cells. By targeting calcineurin, the therapy aims to prevent T-cell-mediated immune responses, lessen kidney inflammation, and prevent further damage to podocytes — specialized kidney cells that work to filter the blood.
AURORA (NCT03021499) evaluated whether adding voclosporin to standard treatment — Genentech’s CellCept (mycophenolate mofetil) and low-dose corticosteroids — could be more effective than standard therapy alone at treating lupus nephritis, a common and serious kidney inflammation in people with systemic lupus erythematosus.
The trial enrolled 357 people with active lupus nephritis. All were randomly assigned to either voclosporin (23.7 mg twice a day) or a placebo in combination with standard care for one year.
The study’s main goal was to assess whether adding voclosporin to standard-of-care increased the proportion of patients achieving kidney response at the end of treatment. Kidney response was defined as a decrease of no more than 20% in estimated glomerular filtration rate (eGFR) — a renal function marker — and a urine protein to creatinine ratio (UPCR) not superior to 0.5 mg/mg. Creatinine is an indicator of kidney function.
Secondary goals included assessing partial responses, and the speed and duration of treatment responses.
The study met all its goals. In total, 40.8% of patients given voclosporin plus standard therapy achieved a complete kidney response, compared to 22.5% of those in the placebo group. This meant that adding voclosporin increased by 2.65 times the likelihood of a complete response.
“We are pleased to report that the patients who received voclosporin were 2.65 times more likely to meet the criteria for response based on proteinuria and eGFR,” Keisha L. Gibson, MD, a professor of medicine and pediatrics at UNC Kidney Center and the trial’s lead investigator, said in a press release.
Those given voclosporin plus standard therapy also lowered their levels of UPCR twice as quickly as patients on standard-of-care alone. The median time for UPCR levels to drop under 0.5 mg/mg was 169 days in the voclosporin plus standard care group, and 372 days in patients given a placebo plus standard care.
A significantly larger proportion of voclosporin-treated patients also achieved partial responses after six and 12 months. Responses were faster among those on the treatment candidate than in patients on placebo.
Benefits were maintained in subgroup analyses, which divided participants according to their age, race, and prior use of CellCept, among other measures; all favored voclosporin plus standard therapy.
Voclosporin’s use was well-tolerated, with no new side effects reported. Serious adverse events were reported in 20.8% of voclosporin-treated patients and in 21.3% of those on standard treatment alone.
Infection was the most common serious adverse event, affecting 10.1% of patients on voclosporin and 11.2% of those in the control group. Six patients died during the study, five on placebo and one in the voclosporin group.
“There were no differences in the safety profile between the voclosporin and standard care groups,” Gibson said.
“These results suggest that the addition of VCS [voclosporin] to MMF [mycophenolate mofetil] and low-dose steroids in active LN [lupus nephritis] patients results in statistically superior and faster renal response rates versus standard of care,” the researchers wrote.
“We know that achieving remission status in lupus kidney disease correlates with good long-term kidney survival, and so the results of this study are very encouraging,” Gibson added.
Voclosporin-treated patients who completed AURORA are eligible to enroll in a two-year extension study, called AURORA 2 (NCT03597464), that runs through August 2021.
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