Adding the experimental oral therapy voclosporin to standard-of-care treatment is safe and nearly doubles the proportion of complete kidney responses in people with lupus nephritis, according to top-line data from a Phase 3 study.
Aurinia Pharmaceuticals, the company developing voclosporin, hopes to make the treatment available to patients in 2021.
“This extraordinary pivotal data confirms voclosporin’s ability to achieve statistically significant improvements in clinically meaningful endpoints for this complex disease, with a comparable safety profile to the current standard of care,” Neil Solomons, MD, Aurinia’s chief medical officer, said in a press release.
Voclosporin is an immunosuppressive treatment designed to work by blocking the activity of calcineurin, an enzyme involved in the activation of immune T-cells. By targeting calcineurin, voclosporin aims to prevent T-cell-mediated immune responses, lessen kidney inflammation, and prevent further damage to podocytes — specialized kidney cells that participate in blood filtration.
These potential effects, along with previous data from a Phase 2b trial (NCT02141672), suggested that adding voclosporin to standard treatment could be more effective than standard therapy alone at treating lupus nephritis, a common and serious kidney inflammation in people with systemic lupus erythematosus.
Participants were randomly assigned to either voclosporin or a placebo in combination with standard treatment — Genentech’s CellCept (mycophenolate mofetil) and low-dose corticosteroids — for one year.
The trial’s primary goal was to assess whether adding voclosporin to standard-of-care increased complete kidney response rates at the end of treatment. Secondary goals included analyzing partial responses, as well as the speed and duration of treatment responses.
Results showed that the study met all its goals.
Adding voclosporin to standard treatment nearly doubled the proportion of patients achieving complete kidney response, compared to those given a placebo (40.8% vs. 22.5%). A significantly larger proportion of voclosporin-treated patients also achieved partial responses after 6 and 12 months of the therapy, and patients on voclosporin showed faster responses than those on placebo.
Similar benefits were also found in all subgroup analyses, which divided participants according to their age, race, and prior use of CellCept, among other parameters.
“Voclosporin is the first novel treatment that has demonstrated therapeutic efficacy for people living with lupus nephritis and today marks an important advance in the treatment of this potentially life-threatening disease,” said Stevan W. Gibson, president and CEO of Lupus Foundation of America.
Voclosporin was well-tolerated, with no new adverse events reported. It did not increase the rate of serious adverse events (20.8%) compared with standard treatment alone (21.3%). Infection was the most common serious adverse event, reported by around 10% of patients on voclosporin and 11% of those in the control group.
Six patients died during the study, five on placebo and one in the voclosporin group. In addition, participants receiving voclosporin showed no adverse events commonly associated with calcineurin suppressors, supporting the therapy’s improved safety profile.
“We are thrilled with the outcomes reported today from the AURORA trial, which unequivocally demonstrate the tremendous potential for voclosporin to play an important role in the treatment of the approximately one million people worldwide living with [lupus nephritis],” said Peter Greenleaf, Aurinia’s president and CEO.
“We are aware of the intense need for a clinically impactful therapy for this serious disease and are working with urgency to complete regulatory filings in the U.S. and worldwide. If approved, we look forward to potentially making voclosporin available to patients beginning in 2021,” Greenleaf added.
Aurinia plans to present further AURORA data at a future scientific conference and to submit a new drug application for voclosporin to the U.S. Food and Drug Administration (FDA) in the first half of 2020.
“These data represent a potential game changer for [lupus nephritis] patients,” said Brad Rovin, MD, chief of the division of nephrology and medical director of the Clinical Trials Management Organization at The Ohio State University Wexner Medical Center.
After completing AURORA, eligible patients may continue treatment under a two-year extension study known as AURORA 2 (NCT03597464), which will assess voclosporin’s long-term safety and effectiveness.