– BLISS-LN achieves primary endpoint and all major secondary endpoints

– On-track for regulatory submission during the first half of 2020

LONDON, UK I December 18, 2019 I GSK today announced positive headline results for intravenous (IV) Benlysta (belimumab) in the largest controlled phase 3 study in active lupus nephritis (LN), an inflammation of the kidneys caused by systemic lupus erythematosus (SLE) which can lead to end-stage kidney disease.

The Efficacy and Safety of Belimumab in Patients with Active Lupus Nephritis (BLISS-LN) study, involving 448 patients, met its primary endpoint demonstrating that a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) over two years 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).

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: “Lupus nephritis is one of the most common and serious complications of SLE, occurring in up to 60% of adult patients. The results of the BLISS-LN study show that Benlysta could make a clinically meaningful improvement to the lives of these patients who currently have limited treatment options.”

Dr Richard Furie, Chief of the Division of Rheumatology and Professor at the Feinstein Institutes at Northwell Health and Lead Investigator of BLISS-LN said: “My journey with Benlysta began nearly twenty years ago when we performed the very first clinical research trial in lupus patients.  To see it culminate in a successful phase 3 lupus nephritis study is a key achievement as the inadequate response of our patients with kidney disease to conventional treatment has long been an area in need of major improvement.”

Belimumab also demonstrated statistical significance compared to placebo across all four major secondary endpoints: Complete Renal Response (CRR) after two years (the most stringent measure of renal response), Ordinal Renal Response (ORR) after two years, PERR after one year, and the time to death or renal-related event. In BLISS-LN, safety results for patients treated with belimumab were generally comparable to patients treated with placebo plus standard therapy. The safety results are consistent with the known profile of belimumab.

Benlysta is currently not recommended for use in severe active lupus nephritis anywhere in the world because it has not been previously evaluated in these patients. Based on these positive phase 3 data, GSK plans to progress regulatory submissions in the first half of 2020 to seek an update to the prescribing information.

The full results will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.

About lupus nephritis
Systemic lupus erythematosus (SLE), the most common form of lupus, is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage. In lupus nephritis (LN), SLE causes kidney inflammation, which can lead to end-stage kidney disease. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis.1,2 Manifestations of LN include proteinuria, elevations in serum creatinine, and the presence of urinary sediment.

BLISS-LN, which enrolled 448 adult patients, was a phase 3, 104-week, randomised, double-blind, placebo-controlled post-approval commitment study to evaluate the efficacy and safety of IV belimumab 10 mg/kg plus standard therapy (mycophenolate mofentil 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 lupus nephritis. Active lupus nephritis was confirmed by kidney biopsy during screening visit using the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, and clinically active kidney disease.

The primary endpoint PERR was defined as estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m2 or no decrease in eGFR from pre-flare of > 20%; and urinary protein:creatinine ratio (uPCR) ≤ 0.7; and not a treatment failure. The most stringent secondary endpoint CRR was defined as eGFR is no more than 10% below the pre-flare value or within normal range; and uPCR < 0.5; and not a treatment failure. ORR was defined as complete, partial or no response.

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

The current US and EU indication for Benlysta are summarised below:

In the US, “Benlysta is indicated for the treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.”

Full US prescribing information including Medication Guide is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF

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

The Precaution and Warnings for Benlysta includes information that “Benlysta has not been studied in the following adult and paediatric patient groups, and is not recommended: severe active central nervous system lupus; severe active lupus nephritis; HIV; a history of, or current, hepatitis B or C; hypogammaglobulinaenia (IgG < 400mg/dl) or IgA deficiency (IgA < 10 mg/dl); a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.”

The EU Summary of Product Characteristics for Benlysta is available on: www.ema.europa.eu

Benlysta is available as an intravenous and a subcutaneous formulation. The Benlysta subcutaneous formulation is not approved for use in children.

GSK’s commitment to immunology
GSK is focused on the research and development of medicines for immune-mediated diseases, such as lupus and rheumatoid arthritis, that are responsible for a significant health burden to patients and society. Our world-leading scientists are focusing research on the biology of the immune system with the aim to develop immunological-based medicines that have the potential to alter the course of inflammatory disease. As the only company with a biological treatment approved for adult and paediatric lupus, GSK is leading the way to help patients and their families manage this chronic, inflammatory autoimmune disease. Our aim is to develop transformational medicines that can alter the course of inflammatory disease to help people live their best day, every day.

SOURCE: GlaxoSmithKline