European Commission approves Benlysta for adult patients with active lupus nephritis

GlaxoSmithKline plc (GSK) today announced the European Commission has approved the expanded use of intravenous and subcutaneous BENLYSTA (belimumab) in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis (LN) in Europe, in addition to systemic lupus erythematosus (SLE). The EU marketing authorisation follows the recent approval for the similar expanded LN indication in the U.S.

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said: “Active lupus nephritis, which causes inflammation in the kidneys, is one of the most serious consequences of systemic lupus erythematosus and occurs in more than 1 million patients worldwide. Benlysta is the first biologic approved to treat lupus and lupus nephritis, representing a significant new treatment option for patients and physicians across Europe dealing with this complex autoimmune disease.”

The marketing authorisation application was based on data from the BLISS-LN (Efficacy and Safety of Belimumab in Adult Patients with Active Lupus Nephritis) study, which showed that, over two years, belimumab added to standard therapy increased renal response rates and helped to prevent worsening of kidney disease in patients with active lupus nephritis compared to standard therapy alone.

The BLISS-LN study is the largest and longest phase 3 study conducted in active LN, involving 448 adult patients. The study met its primary endpoint demonstrating that a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) at two years (or 104 weeks) when treated with belimumab plus standard therapy compared to placebo plus standard therapy in adults with active LN (43% vs 32%, odds ratio (95% CI) 1.55 (1.04, 2.32), p=0.0311). Statistical significance compared to placebo across all four major secondary endpoints was achieved, including Complete Renal Response at Week 104 and Time to Renal-Related Event or Death. The adverse reactions observed in BLISS-LN were consistent with the known safety profile of belimumab administered intravenously plus standard therapy in patients with SLE.

Dr. Y.K.O. (Onno) Teng, MD, PhD, Nephrology clinician-scientist at the Department of Internal Medicine of the Leiden University Medical Center (LUMC), The Netherlands said: “In the BLISS-LN study the addition of Benlysta to standard therapy resulted in a 49% decrease in risk to patients of experiencing a renal-related event as well as a significantly higher number of study participants reaching the PERR. I’m encouraged that progress is being made for people with lupus nephritis as we work toward the overarching goal to delay the need for kidney replacement therapies, such as dialysis and transplantation.” 

Dr. Richard Furie, Chief of the Division of Rheumatology and Professor at the Feinstein Institutes for Medical Research at Northwell Health, and Lead Investigator of the BLISS-LN study commented: “This achievement is derived from decades of research. For years, we have not been able to achieve remission for more than 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. The data from the BLISS-LN study show that Benlysta added to standard therapy in management of active lupus nephritis may lead to improved long-term outcomes for patients by both increasing response rates and delaying further kidney disease progression.”

About the BLISS-LN study
BLISS-LN is a phase 3, 104-week, randomised, double-blind, placebo-controlled, post-approval commitment study to evaluate the efficacy and safety of intravenous (IV) belimumab 10 mg/kg plus standard therapy (mycophenolate mofetil for induction and maintenance, or cyclophosphamide for induction followed by azathioprine for maintenance, plus steroids) compared to placebo plus standard therapy in adult patients with active LN. Active LN was confirmed by renal biopsy during screening visit using the 2003 International Society of Nephrology/Renal Pathology Society criteria within the past 6 months, and clinically active kidney disease requiring induction therapy.^[1]

About lupus nephritis
Systemic lupus erythematosus (SLE), the most common form of lupus, is a chronic, incurable, autoimmune disease. It is difficult to diagnose and even more challenging to treat. The condition is associated with a range of debilitating symptoms that can fluctuate over time, including painful or swollen joints, extreme fatigue, unexplained fever, and skin rashes. In lupus nephritis (LN), SLE causes inflammation (swelling or scarring) of the small blood vessels that filter wastes in the kidney (glomeruli) and sometimes the kidneys, by attacking them like they would attack a disease.^[2] LN can lead to end-stage kidney disease, which could require dialysis or a kidney transplant. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis.^[3],^[4] Manifestations of LN include proteinuria, elevations in serum creatinine and the presence of urinary sediment. Approximately 20% of patients with LN progress to end-stage kidney disease within 10 years of diagnosis.^[1]

About Benlysta (belimumab)
Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Belimumab does not bind to B cells directly or directly deplete B cell populations. By binding BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

In the EU, belimumab was first approved for use as add-on therapy in adults with SLE as an IV formulation in July 2011, and as a subcutaneous (SC) formulation in November 2017. The SLE indication was extended for the use in children for the IV formulation in October 2019:

Benlysta EU Indication
Benlysta IV is indicated as add-on therapy in patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) despite standard therapy.

Benlysta IV is indicated in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis.

Benlysta SC is indicated in the EU as add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus with a high degree of disease activity (e.g., positive anti dsDNA and low complement) despite standard therapy.

Benlysta SC is indicated in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis.

For the EU Summary of Product Characteristics for Benlysta, please visit www.ema.europa.eu.