AstraZeneca's Anifrolumab Granted Clinical Trial Approval in China for Systemic Lupus Erythematosus

Systemic Lupus ErythematosusSystemic lupus erythematosus (SLE) is an autoimmune inflammatory connective tissue disease. From a pathogenic perspective, 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, with the involvement of complement, they induce acute and chronic inflammation and tissue necrosis.

Systemic Lupus Erythematosus (SLE) is the most common (accounting for approximately 70%) and most severe form of lupus. It presents with diverse clinical manifestations, including extensive erythematous rash, fever, pain, renal impairment, and respiratory and nervous system involvement, among others. SLE is a life-threatening serious disease.

Currently, the drugs clinically used for the treatment of systemic lupus erythematosus mainly include glucocorticoids (prednisone, hydrocortisone, betamethasone), immunosuppressants (cyclophosphamide), antimalarial drugs (hydroxychloroquine), and biological agents. These drugs are often accompanied by adverse reactions, especially the long-term use of glucocorticoids, which are commonly used in clinical practice, causing significant harm to the human body.

Therefore, there is a significant unmet clinical need in systemic lupus erythematosus (SLE). Now, good news has arrived! According to the public notice issued by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), the investigational new drug application for anifrolumab injection, submitted by AstraZeneca as a Class 1 therapeutic biological product, has received implicit approval. The drug is intended for the treatment of moderate-to-severe active systemic lupus erythematosus.

Image source: CDE official website

Anifrolumab is a monoclonal antibody that binds to subunit 1 of the type I interferon receptor, thereby antagonizing the activity of all type I interferons (IFN-α, IFN-β, and IFN-ω). Approximately 60%–80% of patients with systemic lupus erythematosus (SLE) exhibit a type I interferon high-expression signature, and type I interferon levels are positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score.

In the previously conducted Phase 3, randomized, double-blind, placebo-controlled trial named TULIP-2, anifrolumab demonstrated positive results. The study enrolled a total of 362 patients with systemic lupus erythematosus (SLE), who were randomized to receive either anifrolumab or placebo on top of existing standard of care, administered once every 4 weeks for 48 weeks.

At 52 weeks, the proportions of patients achieving improvement in the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) index were 47.8% and 31.5% in the anifrolumab and placebo groups, respectively. Anifrolumab resulted in more pronounced BICLA improvement, indicating reduced disease activity across all organ systems without new symptom flares—including fever, joint pain, fatigue, and rash—thereby enabling patients to reduce their required glucocorticoid dosage.

The trial results demonstrated the therapeutic potential of anifrolumab in the treatment of moderate-to-severe systemic lupus erythematosus. However, longer-term studies are still needed to confirm the long-term benefits and safety of anifrolumab.

Other Therapeutic Agents

Belimumab

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 the serum, thereby blocking the binding of BLyS to receptors on B cells. This inhibits B-cell proliferation and their differentiation into plasma cells, ultimately reducing the production of autoantibodies by B cells in the serum and achieving the therapeutic goal in systemic lupus erythematosus (SLE).

In 2011, belimumab was approved by the FDA for adult patients with autoantibody-positive systemic lupus erythematosus (SLE); the initially approved formulation was for intravenous infusion at a dosage of 10 mg/kg.

In 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.

In 2019, the indication for belimumab was expanded, and it was approved by the FDA for pediatric SLE patients aged 5 years and older, becoming the first drug approved in the United States for the treatment of childhood-onset systemic lupus erythematosus (SLE).

In July of the same year, belimumab was approved for marketing in mainland China for use in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who remain highly disease-active despite conventional therapy.

Telitacicept

According to the drug registration progress inquiry results from China’s National Medical Products Administration (NMPA), the application status for market approval of Telitacicept, a Class 1 new drug independently developed by RemeGen, has been updated to “Approval Completed – Pending Certificate Issuance,” with the approval number Guoyao Zhunzi S20210008. This indicates that the new drug has been officially approved in China. According to the priority review public notice issued by the NMPA’s Center for Drug Evaluation (CDE), the indication for this application is systemic lupus erythematosus (SLE). Publicly available information shows that Telitacicept features a novel drug structure and a dual-target mechanism of action. It is the first domestically produced new drug approved in China for the treatment of SLE in over 60 years and is poised to become a “first-in-class” innovative biologic drug in China.

Telitacicept is a TACI-Fc fusion protein that simultaneously targets two cytokines, BLyS and APRIL. These cytokines are key factors in the differentiation and maturation of B lymphocytes. Their overexpression is a significant contributor to various B cell-mediated autoimmune diseases, including systemic lupus erythematosus. Inhibiting BLyS/APRIL can more effectively suppress the immune response, thereby achieving the therapeutic goal of treating autoimmune diseases.

One multicenter, randomized, double-blind, placebo-controlled Phase II clinical study demonstrated that the 48-week Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response rate in the high-dose telitacicept group was significantly higher than that in the placebo control group (79.2% vs. 32.0%), thereby meeting the primary endpoint. The results for secondary endpoints, including serum biomarkers, were consistent with the efficacy outcomes, supporting the primary clinical findings. Telitacicept was well tolerated in terms of safety.

Artemisinin

“Antimalarial efficacy” is unquestionably a renowned milestone for artemisinin. Beyond this, artemisinin and its derivatives have demonstrated promising therapeutic effects in the treatment of immune-related diseases. In June 2019, Tu Youyou’s team officially announced new progress in the use of artemisinin for treating lupus erythematosus. Clinical trials for the indications of dihydroartemisinin in the treatment of systemic lupus erythematosus and discoid lupus erythematosus have been approved. If developments proceed smoothly, the new dihydroartemisinin tablets could receive approval for market launch as early as around 2026.

Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease in which the body’s immune system attacks its own tissues, and there remains a substantial unmet therapeutic need in clinical practice. We look forward to the smooth progress of the aforementioned novel therapies in clinical studies, bringing new treatment options to patients with SLE at an early date.

Reference Source:

1. Eric F. Morand, et al., (2019). Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med, 10.1056/NEJMoa1912196；

2. Clinical Trial Provides 'First Real Hope' of a Lupus Treatment in Half a Century. Retrieved Dec 21, 2019, from https://www.sciencealert.com/clinical-trial-provides-first-real-hope-of-a-lupus-treatment-in-half-a-century；

3. Mathias LM, Stohl W. Systemic lupus erythematosus (SLE): emerging therapeutic targets[J]. Expert Opin Ther Targets. 2020 Dec;24(12):1283-1302.