FDA Expands Belimumab Indication to Adults With Lupus Nephritis

Megan Brooks

December 18, 2020

The US Food and Drug Administration (FDA) has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

"Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease," Hal Barron, MD, GlaxoSmithKline's (GSK's) chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

"Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys" represents a "compelling therapeutic approach to lupus nephritis," the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

"In the four decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one third of patients with lupus nephritis, and despite all of our efforts, 10% to 30% of patients with lupus kidney disease still progress to end-stage kidney disease," Furie, who is chief of the Division of Rheumatology at Northwell Health, notes in the GSK statement.

"The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over two years, but it also prevented worsening of kidney disease in patients with active lupus nephritis compared to standard therapy alone," he added.

BLISS-LN Study: Belimumab Effect Seen Mostly in Those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs 32%; odds ratio [OR], 1.6; 95% CI, 1.0 – 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m2 of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that "most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine."

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

"If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients," observed Ward, who is with the National Institutes of Health, and Tektonidou, of the National and Kopodistrian University, in Athens, Greece.

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