GSK's Benlysta (Belimumab) Approved in the EU and Launched in China for Active Lupus Nephritis

May 06, 2021 /BioValleyBIOON/ --GlaxoSmithKline(GSK) recently announced that the European Commission (EC) has approved Benlysta (Chinese brand name: Beiliteng; generic name: belimumab), both intravenous and subcutaneous formulations, in combination with background immunosuppressive therapy, for the treatment of adult patients with active lupus nephritis (LN). In the United States, Benlysta was approved in December 2020 as the first medication for the treatment of LN, indicated for adult patients with active LN who are receiving standard therapy.

In the United States and the European Union, Benlysta was previously approved for the treatment of systemicLupus Erythematosus(SLE). With the approval of new indications for LN,Benlysta has become the first and only biologic agent approved for the treatment of both SLE and LN., representing this incurableAutoimmunityA significant advancement in the treatment of autoimmune diseases. Data from the BLISS-LN study showed that during 2 years of treatment, compared with standard therapy,Benlysta in combination with standard therapy can increase the renal response rate in patients with active LN, delay the progression of kidney disease, and improve long-term patient outcomes.

Lupus Nephritis (LN) is a form of kidney inflammation caused by systemic lupus erythematosus (SLE) and may progress to end-stage kidney disease (ESKD), necessitating dialysis or kidney transplantation. Worldwide, more than 1 million patients with SLE develop active LN. As one of the most common and severe complications of SLE, LN occurs in up to 40% of SLE patients, causing renal inflammation and potentially leading to end-stage kidney disease.

Notably, in January 2021, the U.S. FDA approved Aurinia Pharmaceuticals’ oral, best-in-class, novel calcineurin inhibitor, Lupkynis (voclosporin), in combination with background immunosuppressive therapy, for the treatment of adult patients with active lupus nephritis (LN). This approval made Lupkynis the firstFDAThe First Approved Oral Therapy for the Treatment of LN.

Benlysta was approved for marketing in 2011 as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in over 50 years. The drug 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 is available in two forms: single-dose pre-filled syringes and single-dose auto-injectors. After receiving training, patients can self-administer the medication via subcutaneous injection, providing an important therapeutic option for the SLE patient population. It should be noted that the SC formulation is indicated only for adults aged ≥18 years and is not suitable for children. Furthermore, Benlysta is not recommended for use in patients with severe active central nervous system lupus or in combination with other biologic agents.

In the United States and the European Union, Benlysta is indicated for the treatment of pediatric (aged ≥5 years) and adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy.

In China, Benlysta (倍力腾, belimumab for injection) was approved in July 2019.As the first biologic agent approved globally for the treatment of SLE, Benlysta is 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 therapy.

Lupus Nephritis (Image source: rheumnow.com)

For the treatment of adult patients with active lupus nephritis (LN), the regulatory approval of Benlysta was based on the results of the BLISS-LN study, the largest and longest Phase III trial conducted in patients with active LN. This was a 2-year (104-week) randomized, double-blind, placebo-controlled, post-marketing commitment study that enrolled a total of 448 patients to evaluate the efficacy and safety of Benlysta (intravenous infusion [IV], 10 mg/kg) plus standard of care (mycophenolate mofetil for induction and maintenance, or cyclophosphamide for induction and azathioprine for maintenance, along with corticosteroids) versus placebo plus standard of care in adult patients with active LN. Active LN was confirmed by kidney biopsy and clinical evidence of active renal 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, partial, or no response.

The results demonstrated that the study met its primary endpoint: after 2 years of treatment, the proportion of patients achieving PERR was 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 showed statistically significant benefits over placebo across four key secondary endpoints, including 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.

SystematicLupus Erythematosus(Systemic Lupus Erythematosus [SLE]) is the most common type of lupus (accounting for approximately 70%), 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 kidney 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. (Bioon.com)

Original Source: European Commissionapproves Benlysta for adult patients with active lupus nephritis