In January 2021, the US FDA approved voclosporin for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Voclosporin, a novel calcineurin inhibitor, has a favorable metabolic profile and a consistent dose-concentration relationship, eliminating the need for therapeutic drug monitoring
Results from the phase 2 AURA-LV and phase 3 AURORA 1 studies demonstrated that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids in patients with lupus nephritis significantly increased rates of complete renal responses at 48 weeks (AURA-LV) and 52 weeks (AURORA-1).
During a presentation at the 59th ERA Congress, Y. K. O. Teng and colleagues reported results of the completed continuation study, AURORA 2. The continuation study examined the long-term safety and tolerability of voclosporin versus placebo in patients with lupus nephritis receiving treatment for an additional 24 months after completion of AURORA 1. The presentation was titled Voclosporin for Lupus Nephritis: Results of the Two-Year AURORA 2 Continuation Study.
Inclusion criteria for the AURORA 1 study were a diagnosis of biopsy proven active lupus nephritis (Class III, IV, or V), proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V), and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2. Patients enrolled in AURORA 1 were eligible to enroll in AURORA 2 and continued with the same blinded treatment of voclosporin (23.7 mg BID) or placebo in combination with MMF (target dose 2 g/day) and low-dose oral steroids. Adverse events and laboratory assessments including eGFR were used to monitor safety and tolerability; changes in urine protein creatinine ratio (UPCR) were also examined.
A total of 116 patients in the voclosporin arm and 100 patients in the control arm were enrolled in AURORA 2. Ninety-two patients in the voclosporin arm (79.3%) and 73 patients in the control arm (73.0%) completed treatment to the end of AURORA 2. Compared with patients in the control arm, there were no new or unexpected safety signals detected in patients in the voclosporin. The rates of serious adverse events were 19.0% in the voclosporin arm and 24.0% in the control arm; in both arms there were eight serious events of infection.
Through the end of the study period, eGFR remained stable. The slopes of least-squares (LS) mean change in corrected eGFR from AURORA 2 baseline to the end of the study were –0.2 in the voclosporin arm and –5.4 in the control arm. There were no deaths in the voclosporin arm and four deaths in the control arm (one due to pulmonary embolism and three due to coronavirus infection). The LS mean reduction in UPCR seen in AURORA 1 were maintained in AURORA 2 with no increase in UPCR at the follow-up visit 4 weeks following discontinuation of the study drug.
In conclusion, the researchers said, “Voclosporin was well tolerated over three years of treatment with a similar safety profile to control and no unexpected safety signals detected. Further, the significant and meaningful reductions in proteinuria initially achieved in AURORA 1 were maintained throughout AURORA 2. These data provide evidence of a long-term treatment benefit of voclosporin in patients with lupus nephritis.”
Source: Teng YKO, Saxena A, Palmen M, Birardi V, Lisk L. Voclosporin for lupus nephritis: results of the two-year AURORA 2 continuation study. Abstract of a presentation at the 59th European Renal Association Congress, Paris, France, May 19-22, 2022.