GSK's Benlysta Receives CHMP Positive Opinion for Active Lupus Nephritis, Already Approved by U.S. FDA

Mar 29, 2021 03:24 CST Updated 03:24

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.

March 28, 2021/BioValleyBIOON/--GlaxoSmithKline(GSK) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of 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). LN is a condition caused by systemicLupus ErythematosusRenal inflammation caused by systemic lupus erythematosus (SLE), which may lead to end-stage kidney disease (ESKD) and require dialysis or kidney transplantation. Worldwide, more than 1 million patients with SLE develop active lupus nephritis (LN).

The CHMP opinion will now be submitted to the European Commission (EC) for review, which typically issues its final decision within two months. If approved, Benlysta will become the first and only biologic agent simultaneously approved in the European Union for the treatment of both SLE and LN. In December 2020, Benlysta received approval from the US FDA for the treatment of adult patients with active LN who are receiving standard therapy. This approval made Benlysta the firstFDAThe first approved drug for the treatment of LN.

LN is one of the most common and severe complications of SLE, occurring in up to 40% of SLE patients. This condition causes 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, representing a breakthrough for this incurableAutoimmunityA Significant Advance in the Treatment of Sexually Transmitted Diseases.

Notably, in January 2021, the U.S. FDA approved Aurinia Pharmaceuticals’ oral, novel, best-in-class 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, becoming 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 process takes approximately one hour. The SC formulation comes in two formats: single-dose pre-filled syringes and single-dose auto-injectors. 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 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 and adult patients aged ≥5 years with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. In China, Benlysta (Belyingteng, belimumab for injection) was approved in July 2019. As the first biologic agent approved globally for the treatment of SLE, Belyingteng is approved in China for use in combination with conventional therapy in adult patients with active, autoantibody-positive SLE who continue to exhibit high disease activity despite conventional therapy.

Lupus Nephritis (Image source: rheumnow.com)

Benlysta has received U.S. approval for the treatment of adult patients with active LNFDARegulatory approvals and the positive opinion from the European Union’s Committee for Medicinal Products for Human Use (CHMP) are both based on results from the BLISS-LN study, the largest and longest Phase III trial conducted in patients with active lupus nephritis (LN). This was a 2-year (104-week), randomized, double-blind, placebo-controlled, post-approval commitment study that enrolled 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 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 the normal range or no more than 10% below pre-flare levels, 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, there was a statistically significant increase in the proportion of patients achieving PERR in the Benlysta plus standard-of-care group compared with 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%), 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 kidney inflammation, which can lead to end-stage renal disease. Although in the past few decades, LN'sDiagnosisBoth treatment and outcomes have improved, but 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: GSK receives CHMP positive opinion recommendingapproval of Benlysta for adult patients with active lupus nephritis