Belimumab, the First New Lupus Drug in 60 Years, Approved in China for Systemic Lupus Erythematosus

Systemic Lupus ErythematosusSystemic lupus erythematosus (SLE) is an autoimmune inflammatory connective tissue disease. From the perspective of pathogenesis, the prevailing view holds that the interaction of various factors, including genetic predisposition, environmental triggers, and estrogen levels, leads to excessive B-cell proliferation in patients. This results in the production of large amounts of autoantibodies, which bind to corresponding self-antigens to form immune complexes. These complexes deposit in the skin, joints, small blood vessels, glomeruli, and other sites, where they trigger acute and chronic inflammation and tissue necrosis with the involvement of complement. Alternatively, antibodies may directly interact with antigens on tissue cells, causing cellular destruction and thereby leading to multi-system damage in the body.

Systemic Lupus Erythematosus (SLE) is the most common (accounting for approximately 70%) and most severe form of lupus erythematosus. It presents with diverse clinical manifestations, including extensive erythematous rash, fever, pain, renal impairment, and respiratory and nervous system involvement. SLE predominantly affects young women, with the highest incidence occurring between the ages of 20 and 40. The prognosis with traditional treatments has been relatively poor. With advancements in therapeutic techniques, the 10-year survival rate has gradually increased from less than 50% to 60%–70%. However, effective treatment options remain limited, and unmet clinical needs are still substantial.

Traditional pharmacological treatments for systemic lupus erythematosus (SLE) have largely consisted of non-selective immunosuppressants aimed at alleviating inflammatory responses, such as aspirin, cyclophosphamide, and glucocorticoids (e.g., prednisone, hydrocortisone, and betamethasone), as well as hydroxychloroquine, which was approved by the U.S. Food and Drug Administration (FDA) in April 1955. It was not until March 9, 2011, that belimumab (brand name Benlysta), an injectable agent developed by GSK, received FDA approval, becoming the first new medication for SLE approved by the FDA in over 50 years and ushering in a new era in the clinical management of SLE.

In fact, since the approval of belimumab, no other drugs have been approved for the treatment of systemic lupus erythematosus (SLE) from 2011 to the present. Belimumab can be considered the first new drug for lupus in 60 years.

On July 2, 2019, GSK’s marketing application for belimumab for injection in China (JXSS1800005/6) was approved by the National Medical Products Administration (NMPA), indicating that this innovative new drug for systemic lupus erythematosus (SLE) would soon be available on the Chinese market.

Belimumab is a first-in-class specific inhibitor of B-lymphocyte stimulator (BLyS, also known as BAFF). It exhibits high affinity for soluble BLyS in serum, thereby blocking the binding of BLyS to receptors on B cells. This inhibits B-cell proliferation and their differentiation into plasma cells, reducing the production of autoantibodies by B cells in the serum, thus achieving the therapeutic goal in systemic lupus erythematosus (SLE).

Belimumab is currently the only marketed BLyS antibody, approved solely for the indication of systemic lupus erythematosus (SLE). Its global sales have maintained steady growth, reaching £473 million in 2018.

Belimumab was first approved by the FDA on March 9, 2011, for adult patients with autoantibody-positive systemic lupus erythematosus (SLE). The initially approved formulation was for intravenous infusion at a dose of 10 mg/kg, administered once every two weeks for the first three doses, followed by once every four weeks thereafter, with each infusion lasting one hour.

On July 20, 2017, the subcutaneous formulation of belimumab was approved by the FDA for adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. The dosage is 200 mg administered once weekly. The short administration time allows for self-administration by patients, thereby enhancing convenience.

On April 27, 2019, the indication for belimumab was expanded, with FDA approval for use in pediatric SLE patients aged 5 years and older, making it the first drug approved in the United States for childhood SLE.

Belimumab can significantly reduce the 52-week Systemic Lupus Erythematosus Responder Index (SRI) in patients with SLE and reduce disease flares. At the 2017 European League Against Rheumatism (EULAR) annual meeting, GSK presented the results of a 10-year clinical study on belimumab for the treatment of active SLE. A total of 298 patients were enrolled in the long-term extension study, and at year 10, 131 patients (44%) remained in the study. The results showed that the proportion of patients achieving remission with belimumab treatment gradually increased over time, with an overall remission rate of 65.2% (n=126) at year 10. Among patients whose baseline prednisone dose exceeded 7.5 mg/day, 32.6% (14/43) reduced their dose to ≤7.5 mg/day by year 10; among those whose baseline prednisone dose was ≤7.5 mg/day, 9.5% (9/95) increased their dose to >7.5 mg/day by year 10.

Accurate data on the number of patients with lupus erythematosus in China are currently unavailable. A large-scale survey (with a sample size >30,000) indicated that the prevalence of systemic lupus erythematosus (SLE) in China is 70 per 100,000 individuals, reaching as high as 113 per 100,000 among women (Source: 2010 Guidelines for the Diagnosis and Treatment of Systemic Lupus Erythematosus). Belimumab can alleviate patient symptoms, reduce disease flares, and improve long-term prognosis. The approval of belimumab for marketing in China through the priority review pathway will provide a new treatment option for Chinese SLE patients. The drug’s approval timeline in China also reflects the National Medical Products Administration’s (NMPA) emphasis on this urgently needed clinical therapy; only one day elapsed between the “initiation of administrative review by the NMPA” and the “completion of review, pending certificate issuance.”

There are not many global research projects targeting BLyS. According to the data included in NextPharma by Medicine Cube, the only BLyS project with publicly available information in China is UBP1213, developed by Zhonghe Pharmaceutical and Junshi Biosciences.

However, there are relatively many new drug projects targeting systemic lupus erythematosus (SLE) in China, with a diverse range of targets including BTK, CRBN, CD20, and PKCβ. This also includes the star project dihydroartemisinin, licensed by Kunming Pharmaceutical Group from the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, which was the focus of recent headline news. We look forward to breakthroughs by domestic companies in addressing this life-threatening disease.

Original Title: The First New Drug for Lupus Erythematosus in 60 Years, "Belimumab," Approved for Market Launch in China