The calcineurin inhibitor voclosporin has shown superior complete remission rates among lupus nephritis patients taking 23.7 mg (considered a low dose) of the drug, twice daily.
This is the first global lupus nephritis study to meet the primary endpoint of achieving superior complete remission in the low-dose group, according to research by Mary Anne Dooley, M.D., of Dooley Rheumatology, Chapel Hill, NC, and colleagues, which was presented at the American College of Rheumatology annual meeting held in Washington, D.C. on Nov. 15.
Researchers reported on results from the Aurinia Urine Protein Reduction in Active Lupus Nephritis (AURA) study of 265 active lupus nephritis subjects in more than 20 countries. Patients were randomized to a low-dose voclosporin group, high-dose (39.5 mg, twice daily) voclosporin arm or placebo. All subjects also received 2g daily of mycophenolate mofetil (MMF) and low-dose steroids, with a protocol of 20 to 25 mg on day one, tapered down to 5 mg at week eight and 2.5 mg daily at weeks 16 to 24.
Among the study’s objectives at week 24, complete remission, defined as a protein/creatinine ratio of less than or equal to 0.5 mg/mg and an estimated glomerular filtration rate (eGFR) of 60 mL/min or more without a decrease of 20 percent or more. Other outcomes measures were time to complete remission; partial remission, defined as 50 percent reduction in proteinuria; and time to partial remission.
The researchers found superior complete remission rates in the low dose arm, and statistically significant improvement in time to complete remission, as well as time to partial remission, in the low- and high-dose treatment arms. By week six, they noted an increasing complete remission in the voclosporin groups, compared to controls. Subjects in the low-dose arm were about twice as likely to achieve complete remission at 24 weeks, compared to controls.
Subjects in both active groups had a 0.2 mg/dL mean reduction in serum creatinine. Blood pressure was similar among groups. But more than 90 percent of those in the study had at least one adverse event, including the most common infection, followed by gastrointestinal disorders. Subjects in the voclosporin groups were more likely to experience severe adverse events, including death. There were three deaths from infection in the low-dose group, compared to one in the high-dose group and none in the control group; however, the authors consider these unrelated to drug exposure.
The structure of this therapeutic immunomodulating drug candidate, which blocks IL-2 expression and T-cell mediated immune responses, allows for less pharmacokinetic-pharmacodynamic variability. This could offer patients a better drug safety profile compared to other calcineurin inhibitors, the authors write.
“These promising data will be used to plan subsequent studies of voclosporin in [lupus nephritis],” the authors wrote.
Most of the study’s authors report ties to Aurinia Pharmaceuticals, a late stage biopharmaceutical company focused on the development of voclosporin for the treatment of lupus nephritis.
“Speed of Remission with the Use of Voclosporin, MMF and Low Dose Steroids: Results of a Global Lupus Nephritis Study,” Dooley MA, Pendergraft W III, et al. ACR 2016 Abstract Number 5L. 4:30 p.m., Nov. 15, 2016.