Background/Purpose: Unlike in many other disease states, there is no accepted definition for clinical response in lupus nephritis (LN). The Phase 3 AURORA 1 study of voclosporin (VCS) used complete renal response at 52 weeks (CRR; UPCR ≤0.5 g/g, stable eGFR, low-dose steroids, and no rescue medications) as the primary efficacy endpoint.¹  Significantly more patients treated with VCS in combination with MMF and low-dose glucocorticoids (GCs) achieved CRR compared to patients in the control arm treated with MMF and low-dose GCs  (41% vs 23%, odds ratio [OR] 2.65, 95% confidence interval [CI] 1.64-4.27, p< 0.0001). Patients who completed AURORA 1 and elected to continue treatment in the AURORA 2 continuation study demonstrated maintained efficacy and stable renal function up to 36 months.²

In 2024, following the completion of AURORA 2, the US FDA compared the efficacy benefit of VCS to control using a new longitudinal endpoint, sustained complete renal response (SCRR), defined as achieving CRR at Month 12 of AURORA 1 and maintaining the response at each subsequent study visit through the end of AURORA 2 (Month 36). This new endpoint was incorporated into the recently updated labeling for VCS, and results of the analysis are presented here.³ 

Methods: Patients completing AURORA 1 were eligible to enter AURORA 2 on the same blinded therapy (VCS or placebo) combined with MMF (target of 2 g/d) and GCs (20-25 mg/day tapered to 2.5 mg/d by Week 16) for an additional two years. Only patients who continued in AURORA 2 (N=216) were analyzed for SCRR, although all patients who initiated treatment in AURORA 1 (N=357) were included in the denominator of the efficacy analysis. Patients with missing data at AURORA 2 study visits were considered non-responders.

Results: Of the 179 VCS- and 178 control-treated patients enrolled in AURORA 1, 116 (64.8%) and 100 (56.2%) patients, respectively, continued treatment in AURORA 2. Of these patients, 39 (21.8%) and 41 (23.0%), respectively, had missing data and were considered non-responders. At Month 36, 36 (20.1%) of 179 VCS-treated patients and 21 (11.8%) of 178 control-treated patients achieved SCRR (OR 1.99, 95% CI 1.10, 3.62; p=0.0239), with a probability difference between the two groups of 0.087 (95% CI 0.084, 0.09). Additionally, 10.1% of VCS and 9.0% of control-treated patients achieved CRR at all but one study visit (Table 1).

Conclusion: SCRR is a novel endpoint that can be leveraged to illustrate disease trajectory of LN and treatment efficacy. Consistent with using CRR as an efficacy endpoint in AURORA 1, more VCS- than control-treated patients achieved SCRR, despite nearly 40% of the analyzed study population being ineligible due to the voluntary nature of AURORA 2 participation. The stringency and potential utility of this new endpoint require further exploration.

This work was funded by Aurinia Pharmaceuticals Inc.

1.            Rovin BH, et al. The Lancet. 2021; May 29;397(10289):2070-2080. DOI: 10.1016/S0140-6736(21)00578-X.

2.            Saxena A, et al. Arthritis Rheumatol. 2024; Jan;76(1):59-67. doi: 10.1002/art.42657. Epub 2023 Sep 15.

3.            LUPKYNIS [package insert]. Rockville, MD: Aurinia Pharma US, Inc.; 2021. Revised: 4/2024.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rates-of-sustained-complete-renal-response-with-long-term-use-of-voclosporin-in-aurora-2/