FDA Approvals: Lupus Nephritis

Lupus nephritis is one of the leading causes of mortality for patients with systemic lupus erythematosus (SLE), and patients with both SLE and end-stage renal disease have standardized mortality ratios more than 60 times that of patients with SLE with normal kidney function.¹

The good news: Rheumatologists now have not one, but two approved options to treat patients with active lupus nephritis.

Belimumab Approved

In late December 2020, the U.S. Food & Drug Administration (FDA) approved belimumab (Benlysta) to treat adults with active lupus nephritis who are receiving standard therapy. This approval is for both the intravenous and subcutaneous formulations. Belimumab, which was approved by the FDA to treat SLE in March 2011, is now the first agent approved to treat both SLE and active lupus nephritis in adults.²

This approval addresses an unmet need for lupus nephritis patients and is the result of an FDA breakthrough therapy designation and priority review of findings from the BLISS-LN study.³

Background: BLISS-LN was a phase 3 study conducted in patients with active lupus nephritis (N=448). This randomized, double-blind, placebo-controlled, post-approval commitment study evaluated the efficacy and safety of intravenous belimumab (10 mg/kg dose) and standard therapy (i.e., mycophenolate mofetil for remission induction and remission maintenance, or cyclophosphamide for remission induction followed by azathioprine for remission maintenance, and steroids) compared with placebo and standard therapy in this patient population.

The study’s primary end point was a statistically significant greater number of patients with lupus nephritis taking belimumab and standard therapy achieving a primary efficacy renal response at year 2 (week 104) than patients taking placebo and standard therapy (43% vs. 32%; odds ratio: 95% confidence interval [CI] 1.55 (1.04, 2.32), P=0.0311). Additionally, all four major secondary end points, including complete renal response and time to renal-related events or death, achieved statistical significance. No new safety signals were reported.

In BLISS-LN, belimumab with standard therapy significantly improved the signs and symptoms of lupus nephritis, and patients had a 49% decreased risk of a renal-related event.

Voclosporin Also Approved

In January 2021, the FDA approved voclosporin (Lupkynis), a calcineurin inhibitor, to be used in combination with background immunosuppressive therapy to treat adults with active lupus nephritis.^4,5 This treatment, which received an FDA fast track designation in 2016, was approved under priority review and is the first FDA-approved oral therapy for lupus nephritis available in the U.S.

In clinical trials, voclosporin demonstrated significantly improved renal response rates compared with mycophenolate mofetil and low-dose steroids. Voclosporin-treated patients were more than twice as likely to have a decline in their urinary protein creatinine ratio than patients on standard therapy alone. Additionally, this improvement occurred twice as fast in voclosporin-treated patients than in patients treated with standard therapy.

Background: The U.S. approval of voclosporin was based on multi-national clinical trials, including the AURORA-1 phase 3 and AURA-LV phase 2 studies.6-8 Voclosporin’s label carries a boxed warning, stating that patients taking the treatment may have an increased risk for developing
lymphomas and other malignancies, particularly of the skin, and serious infections. The risk appears to be related to increasing doses and duration of immunosuppression rather than to the use of any
specific agent.⁵

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Mok CC, Kwok RC, Yip PS. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 2013
   Aug;65(8):2154–2160.
2. FDA approves GSK’s Benlysta as the first medicine for adult patients with active lupus nephritis in the U.S. [news release] GlaxoSmithKline plc. 2021 Dec 17.
3. Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020 Sep 17;383(12):1117–1128.
4. FDA Approves Aurinia Pharmaceuticals’ Lupkynis (voclosporin) for adult patients with active lupus nephritis. [news release] Aurinia Pharmaceuticals Inc. 2021 Jan 22.
5. Highlights of prescribing information: Lupkynis (voclosporin) capsules. U.S. Food & Drug Administration. 2021 Jan 22. https://tinyurl.com/yg6mdab6.
6. Ginzler EM, Kaplan J, Lisk L, et al. Integrated efficacy of the AURORA 1 and AURA-LV trials
   confirms voclosporin rapid proteinurea reduction in the presence of low-dose steroids [abstract 1843]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).
7. Rovin BH, Solomons N, Pendergraft WF 3rd, et al. A randomized, controlled double-blind study
   comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int. 2019 Jan;95(1):219–231.
8. Arriens C, Polyakova S, Adzerikho I, et al. Aurora phase 3 study demonstrates voclosporin statistical superiority over standard of care in lupus nephritis (LN) [abstract OP0277]. Ann Rheum Dis. 2020;79(Suppl 1):172–173.

Excerpted from https://www.therheumatologist.org/article/fda-approvesbelimumab-voclosporin-for-lupus-nephritis.