Treatment with the investigational calcineurin inhibitor voclosporin is associated with a significant, threefold-higher rate of complete remission for lupus nephritis, compared with the current standard of care, according to 48-week data from the AURA-LV (Aurinia Urinary Protein Reduction Active–Lupus With Voclosporin) study.
In a company release , manufacturer Aurinia Pharmaceuticals presented the results of the international phase IIb controlled trial involving 265 patients with active lupus nephritis from 20 countries, which they say has now met its primary and secondary endpoints.
Participants were allocated either to high-dose (39.5 mg twice daily), to low-dose (23.7 mg twice daily) voclosporin plus mycophenolate mofetil as background therapy and a forced steroid taper, or to a control group of mycophenolate mofetil and a forced steroid taper alone. All groups also received low doses of corticosteroids as background therapy.
After 48 weeks, 49% of patients in the low-dose group and 40% in the high-dose group had achieved complete remission, compared with 24% in the control group (P less than .001 for low-dose vs. control; P = .026 for high-dose vs. control). This represented a threefold-higher remission rate for the low-dose group (odds ratio, 3.21) and a twofold-higher rate for the high-dose group (OR, 2.1), compared with controls.
Complete remission was defined as a composite endpoint that included urine protein/creatinine ratio of 0.5 mg/mg or less; normal, stable renal function; presence of sustained, low dose steroids; and no administration of rescue medications.
Partial remission – defined as at least a 50% reduction in urine protein/creatinine ratio with no concomitant use of rescue medication – was seen in 68% of patients in the low-dose voclosporin group, 72% of patients in the high-dose group, and 48% of patients in the control arm (P = .007 for low-dose vs. control; P = .002 for high-dose vs. control).
Investigators said there were no unexpected safety signals from voclosporin, but there were three deaths and one malignancy reported in the control arm after the study treatment period ended.
Brad Rovin, MD , of Ohio State University in Columbus said in the company’s statement that current treatments for this severe complication of systemic lupus erythematosus are toxic, and complete renal response rates are low.
“The AURA trial’s long-term results convincingly demonstrate that the addition of voclosporin to standard of care treatment is superior to standard of care alone,” Dr. Rovin said. “This is an impressive renal response rate, and these results may shift the treatment paradigm of lupus nephritis.”
Aurinia’s chief medical officer, Neil Solomons, MD , said in the release that the results provide the company with confidence that they can now execute a successful phase III program.
The 24-week results of the study – in which all primary and the 24-week secondary endpoints were also met – were released in November 2016.
