GSK's Benlysta (Belimumab) Achieves Positive Phase III Results in Lupus Nephritis and Gains Approval in China

December 19, 2019/BioonBIOON/--UK pharmaceutical giantGlaxoSmithKline(GSK) recently announced positive results from the BLISS-LN study, the largest controlled Phase III trial of intravenous (IV) Benlysta (Chinese brand name: Beiliteng; generic name: belimumab) for the treatment of active lupus nephritis (LN). LN is a condition caused by systemicLupus Erythematosus(SLE)-induced renal inflammation can lead to end-stage renal disease.

This was a 2-year (104-week), randomized, double-blind, placebo-controlled, post-marketing commitment study that enrolled 448 patients to evaluate the efficacy and safety of Benlysta (IV, 10 mg/kg) plus standard of care (mycophenolate mofetil for induction and maintenance, or cyclophosphamide for induction and azathioprine for maintenance, plus corticosteroids) versus placebo plus standard of care in adult patients with active lupus nephritis (LN). Active LN was confirmed by renal biopsy and clinical evidence of active kidney disease at the screening visit, according to the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification criteria.

The primary endpoint of the study was the Primary Efficacy Renal Response (PERR), defined as: estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m², or a decline in eGFR of no more than 20% from pre-flare levels; urine protein-to-creatinine ratio (uPCR) ≤0.7; and absence of treatment failure. The most stringent secondary endpoint, Complete Renal Response (CRR), was defined as: eGFR within normal range or no more than 10% below pre-flare values, uPCR <0.5, and absence of treatment failure. Ordinal Renal Response (ORR) was defined as complete response, partial response, or no response.

The results showed that the study met its primary endpoint: after 2 years of treatment, the proportion of patients achieving PERR was statistically significantly higher in the Benlysta plus standard-of-care group than in the placebo plus standard-of-care group (43% vs. 32%; odds ratio [95% CI] = 1.55 [1.04, 2.32]; p = 0.0311). Furthermore, Benlysta demonstrated statistically significant benefits over placebo across four key secondary endpoints: complete renal response (CRR, the most stringent measure of renal response) at 2 years, ordinal renal response (ORR) at 2 years, PERR at 1 year, and time to death or renal-related events. In this study, the safety profile of the Benlysta plus standard-of-care group was generally comparable to that of the placebo plus standard-of-care group. The safety findings were consistent with the known safety profile of Benlysta.

Currently, Benlysta is not recommended for patients with severe active lupus nephritis (LN) because the drug has not previously been evaluated in this patient population. Based on the positive results from this Phase III study, GSK plans to advance regulatory submissions in the first half of 2020 to seek updates to the prescribing information. The full results of the study will be presented at an upcoming medicalMeetingand published in peer-reviewed journals.

Dr. Hal Barron, Chief Scientific Officer and President of Research and Development at GSK, stated: “Lupus nephritis is a systemicLupus Erythematosus"One of the most common and serious complications occurs in up to 60% of adult patients. The results of the BLISS-LN study indicate that Benlysta can bring clinically meaningful improvements to the lives of these patients, who currently have limited treatment options."

SystemicLupus Erythematosus(SLE) is the most common type of lupus (accounting for approximately 70%), which is a chronic, incurableAutoimmunityautoimmune disease, accompanied by a series of symptoms that fluctuate over time, including joint pain or swelling, extreme fatigue, unexplained fever, rash, and organ damage. In lupus nephritis (LN), systemicLupus Erythematosus(SLE) causes renal inflammation, which can lead to end-stage renal disease. Although in the past few decades, LN'sDiagnosisAlthough both treatment and outcomes have improved, it remains an indicator of poor prognosis. Manifestations of LN include proteinuria, elevated serum creatinine, and the presence of urinary sediment.

Benlysta is the first specific inhibitor of B lymphocyte stimulator (BLyS), capable of blocking the binding of soluble BLyS (a B-cell survival factor) to BLyS receptors on B cells. Benlysta does not bind directly to B cells; however, by binding to BLyS, it inhibits the survival of B cells (including autoreactive B cells) and reduces their differentiation into plasma cells that produce immunoglobulins. Benlysta can reduce the number of abnormal B lymphocytes that exacerbate lupus symptoms. These abnormal B lymphocytes cause the immune system to mistakenly attack blood vessels and other healthy tissues, leading to lupus and other autoimmune diseases.

Benlysta is the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in over 50 years. It is available in two formulations: intravenous (IV) and subcutaneous (SC). The IV formulation is administered via infusion once every four weeks, with the dose adjusted based on body weight (10 mg/kg), and the infusion takes approximately one hour. The SC formulation comes in two formats: single-dose pre-filled syringes and single-dose autoinjectors. After receiving training, patients can self-administer the subcutaneous injection, providing an important therapeutic option for the SLE patient population. It should be noted that the SC formulation is not suitable for children.

In the United States and the European Union, Benlysta is indicated for the treatment of pediatric and adult patients aged ≥5 years with active, autoantibody-positive systemic lupus erythematosus (SLE). In China, Benlysta (BeiLiteng; belimumab for injection) was approved this July. As the first biologic agent approved globally for the treatment of SLE, BeiLiteng has now been approved in China for use in combination with standard therapy in adult patients with active, autoantibody-positive SLE who continue to exhibit high disease activity despite standard treatment. (Bioon.com)

Original Source:GSK announces positive headline results in phase 3 study of Benlysta in patients with lupus nephritis