GlaxoSmithKline (GSK) recently announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive review suggesting the approval of Benlysta (Chinese trade name: Beliteng, generic name: belimumab, Belyumumab) intravenous preparations and subcutaneous preparations, combined with immunosuppressive therapy, for the treatment of adult patients with active lupus nephritis (LN). LN is a type of kidney inflammation caused by systemic lupus erythematosus (SLE) and may lead to end-stage kidney disease (ESKD), which may require dialysis or kidney transplantation. In the world, there are more than 1 million cases of SLE patients with active LN.

Now, the opinion of CHMP will be submitted to the European Commission (EC) for review, which usually makes a final review decision within 2 months. If approved, Benlysta will become the first and only biologic in the EU to be approved for the treatment of SLE and LN at the same time. In December 2020, Benlysta was approved by the US FDA for the treatment of adult patients with active LN who are receiving standard treatment. This approval makes Benlysta the first drug approved by the US FDA for the treatment of LN.

LN is one of the most common and serious complications of SLE. It occurs in up to 40% of SLE patients. This disease can cause kidney inflammation and may lead to end-stage renal disease. Benlysta is the first drug approved for the treatment of adult patients with SLE and active LN, and represents an important advance in the treatment of this incurable autoimmune disease.

It is worth mentioning that in January 2021, the US FDA approved Aurinia Pharmaceuticals' oral new best-in-class calcineurin inhibitor Lupkynis (voclosporin), combined with a background immunosuppressive treatment plan, for the treatment of adult patients with active LN . This approval makes Lupkynis the first oral therapy approved by the US FDA for the treatment of LN.

Benlysta was approved for marketing in 2011 and is the first new drug approved for the treatment of SLE in the past 50 years. The drug has two dosage forms: intravenous (IV) and subcutaneous (SC). The IV dosage form is intravenously infused every 4 weeks, and the dosage is adjusted according to body weight (10mg/kg), which takes about 1 hour. There are two forms of SC dosage form: single-dose prefilled syringe and single-dose auto-injector. Patients can self-administer subcutaneous injection after training. This dosage form will provide an important treatment option for SLE patients. It should be pointed out that the SC preparation is only suitable for adults aged ≥18 years, not for children. In addition, Benlysta is not recommended for severely active central nervous system lupus or in combination with other biological agents.

In the United States and the European Union, in the treatment of SLE, Benlysta is suitable for the treatment of children and adults with SLE who are receiving standard treatment, aged ≥5 years and positive for active autoantibodies. In China, Benlysta (Benlysta, beliyuumab for injection) was approved in July 2019. As the world's first biological agent approved for the treatment of SLE, Britton has been approved in China to be combined with conventional treatment, which is suitable for active and autoantibody-positive adult patients with SLE who still have high disease activity on the basis of conventional treatment.

For the treatment of adult patients with active LN, Benlysta's regulatory approval from the US FDA and the positive review of the EU CHMP are based on the results of the largest and longest phase III BLISS-LN study in patients with active LN. This is a 2-year (104 weeks) randomized, double-blind, placebo-controlled, post-marketing commitment study. A total of 448 patients were enrolled and Benlysta (intravenous infusion [IV], 10mg/kg) combined Efficacy and safety of standard therapy (mycophenolate mofetil for induction and maintenance, or cyclophosphamide induction, azathioprine maintenance, and endosterol), placebo combined with standard therapy for the treatment of active LN adult patients. Active LN was diagnosed by kidney biopsy and clinically active kidney disease during the screening visit in accordance with the 2003 International Society of Nephrology/ Renal Pathology (ISN/RPS) standards.

The primary endpoint of the study is the primary therapeutic renal response (PERR), which is defined as: glomerular filtration rate (eGFR) ≥60ml/min/1.73m2, or eGFR decreased by no more than 20% from before the flare; urine protein: creatinine ratio ( uPCR)≤0.7; and it is not a treatment failure. The most stringent secondary endpoint of complete renal response (CRR) is defined as: eGFR is less than the pre-flare value by no more than 10% or within the normal range, uPCR<0.5, and it is not a treatment failure. Ordinal Renal Response (ORR) is defined as complete, partial, and no response.

The results showed that the study reached the primary endpoint: after 2 years of treatment, compared with the placebo + standard therapy treatment group, the Benlysta + standard therapy treatment group had a statistically significant increase in PERR patients (43% vs 32%, odds ratio [ 95%CI]=1.55[1.04,2.32], p=0.0311). In addition, Benlysta also showed statistical significance compared with placebo in 4 key secondary endpoints, including: complete renal response (CRR, the most stringent measure of renal response) after 2 years, and ordered renal response after two years Response (ORR), PERR after one year, time to death, or kidney-related events. In this study, the safety results of the Benlysta + standard therapy treatment group are usually comparable to the results of the placebo + standard therapy group. The safety results are consistent with the known Benlysta profile.

Systemic lupus erythematosus (SLE) is the most common type of lupus (approximately 70%), which is a chronic, incurable autoimmune disease, accompanied by a series of symptoms, these symptoms over time Fluctuations include joint pain or swelling, extreme fatigue, unexplained fever, skin rash, and organ damage. In lupus nephritis (LN), systemic lupus erythematosus (SLE) causes inflammation of the kidneys, which can lead to end-stage renal disease. Although the diagnosis and treatment of LN have improved in the past few decades, it is still an indicator of poor prognosis. The manifestations of LN include proteinuria, elevated serum creatinine, and the presence of urine sediment.

Benlysta is the first specific inhibitor of B lymphocyte stimulator (BLyS), which can block the binding of soluble BLyS (a B cell survival factor) to the BLyS receptor on B cells. Benlysta does not directly bind to B cells, but by binding to BLyS, Benlysta can inhibit the survival of B cells (including autoreactive B cells) and reduce the differentiation of B cells into plasma cells that produce immunoglobulins. Benlysta can reduce the number of abnormal B lymphocytes that make lupus worse. These abnormal B lymphocytes can cause cells produced by the immune system to mistakenly attack blood vessels and other healthy tissues, causing lupus and other immune system diseases.

Original source: GSK receives CHMP positive opinion recommending approval of Benlysta for adult patients with active lupus nephritis