Phase 3 Trial Confirms Efficacy and Safety of Voclosporin in Lupus Nephritis

The novel calcineurin inhibitor voclosporin demonstrated greater efficacy and comparable safety in achieving complete renal response in combination with mycophenolate mofetil (MMF) and low-dose steroids when compared to MMF and steroids alone, among patients with lupus nephritis (LN), according to results of the AURORA-1 clinical trial.

Researchers conducted the multicenter, double-blind, randomized phase 3 trial in 142 hospitals and clinics in 27 countries. The study cohort included patients who had been diagnosed with systemic lupus erythematosus (SLE) and LN, according to the American College of Rheumatology criteria, who had undergone a kidney biopsy within 2 years that showed class III, IV, or V LN. Patients were randomly assigned 1:1 to receive only mycophenolate mofetil 1 g twice daily and rapidly tapered low-dose oral steroids (n=179), or to also receive oral voclosporin 23.7 mg twice daily along with MMF and steroids (n=178). The study ran from April 13, 2017, through October 10, 2019.

The primary endpoint was complete renal response at 52 weeks, defined as a composite of urine protein creatinine ratio of 0.5 mg/mg or less; stable renal function, defined as an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73m2 or no confirmed decrease from baseline eGFR of >20%; no rescue medication required; and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or 7 or more days total during Week 44 through Week 52.

Among patients in the voclosporin group, 73 of 178 (41%) patients achieved the primary endpoint of complete renal response at Week 52 vs 40 [23%] of 178 patients in the placebo group (odds ratio, 2.65; 95% confidence interval [CI] 1.64-4.27; P < 0·0001).

Serious adverse events were virtually identical between the 2 groups, occurring in 37 (21%) patients among those receiving voclosporin and 38 (21%) in the placebo group. The most frequent serious adverse event involving infection was pneumonia and again was virtually identical, presenting among 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group.

There were 6 deaths during the study or study follow-up period—1 patient (<1%) in the voclosporin group and 5 [3%] patients in the placebo group. The investigators concluded that no deaths were related to the study treatments.

“Voclosporin in combination with mycophenolate mofetil (MMF) and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile,” the authors wrote. “This finding is an important advancement in the treatment of patients with active LN.”

--Rebecca Mashaw

Reference:

Rubio J ,Kyttaris V. Journal club: efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomized, multicenter, placebo-controlled, phase 3 trial. ACR Open Rheumatol. 2021;3(12):827-831. doi: 10.1002/acr2.11338