Belimumab for Pediatric Systemic Lupus Erythematosus Nears Accelerated Approval in China

Text | Dopine

On April 14, the CDE website indicated that belimumab, GlaxoSmithKline’s (GSK) drug for systemic lupus erythematosus (SLE), was proposed for inclusion in the priority review program, with the rationale being “inclusion in the priority review program under Category II, Item 6: pediatric drugs.” Based on the clinical trials of belimumab applied for in China, the author speculates that the indication sought in this application is pediatric systemic lupus erythematosus.

Lupus erythematosus is an autoimmune inflammatory connective tissue disease, with systemic lupus erythematosus (SLE) being the most common (accounting for approximately 70%) and most severe form. SLE presents with diverse clinical manifestations, including extensive erythematous rash, fever, pain, renal impairment, and respiratory and neurological involvement. It predominantly affects young women, with the highest incidence occurring between the ages of 20 and 40 years. However, SLE tends to follow a more aggressive and severe course in children than in adults.

With the advancement of medical technology, the 10-year survival rate for patients with systemic lupus erythematosus (SLE) has gradually increased from less than 50% to 60–70%; however, the disease remains incurable. Currently, the mainstay of clinical pharmacotherapy for SLE includes glucocorticoids (prednisone, hydrocortisone, betamethasone), immunosuppressants (cyclophosphamide), antimalarial agents (hydroxychloroquine), and belimumab, which has been approved in recent years.

Belimumab (Benlysta) is a specific inhibitor of B-lymphocyte stimulator (BLyS, also known as BAFF) developed by GSK. It binds to soluble BLyS in the serum, thereby blocking the interaction between BLyS and its 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 for systemic lupus erythematosus (SLE).

The drug was first approved by the FDA in March 2011 for the treatment of adult patients with autoantibody-positive systemic lupus erythematosus (SLE), becoming the first new medication for lupus approved globally in nearly 60 years. Last April, the FDA further expanded its indications to include pediatric patients aged 5 years and older.

Since its market launch, sales of belimumab have continued to rise, reportedly reaching $790 million in 2019. With the expansion of the indicated population, sales are expected to reach new highs.

Furthermore, it is worth noting that belimumab has been approved in two formulations: intravenous infusion and subcutaneous injection. The dosage and administration frequency differ between these formulations. The intravenous formulation was approved first, with a dosage of 10 mg/kg administered once every 2 weeks for the first three doses, followed by once every 4 weeks thereafter. The subcutaneous formulation is administered at a dose of 200 mg once weekly.

In China, belimumab was approved relatively late; it was not until July last year that the NMPA approved it for adult patients with active, autoantibody-positive SLE who are receiving standard therapy. Its brand name is Benlysta, and the only approved formulation is for intravenous injection.

According to the Insight database, the price of belimumab is RMB 1,976 per vial (120 mg), which is not excessively high. Moreover, research data indicate that among Asian patients with systemic lupus erythematosus (SLE), particularly in China, treatment with Benlysta in combination with conventional therapy for 52 weeks achieved a maximum SLE Responder Index (SRI) composite response rate of 57.8%, reduced the risk of severe flare by 50%, and significantly decreased patients’ reliance on corticosteroids while maintaining disease stability. The author anticipates that Benlysta will likely further increase its market share in China by leveraging its efficacy and expanding indications.

When discussing systemic lupus erythematosus (SLE), two drugs in China deserve special mention: Telitacicept and Artemisinin. Telitacicept is a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein independently developed by RemeGen Co., Ltd. with full intellectual property rights. It inhibits the proliferation of B lymphocytes and the maturation of T lymphocytes by blocking two bioactive molecules, BLyS and APRIL, thereby suppressing excessive immune responses to achieve the therapeutic goal for SLE. In June last year, the pivotal clinical trial of Telitacicept for the treatment of SLE was successfully completed and met its primary endpoints; it is currently in the stage of applying for market approval. Artemisinin, on the other hand, is a novel antimalarial drug extracted from *Artemisia annua* by Tu Youyou’s team in China. Following structural modification, it has been developed for use in the field of autoimmune diseases. Existing studies indicate that Dihydroartemisinin demonstrates an efficacy rate of over 90% for discoid lupus erythematosus and over 80% for SLE, showing significant therapeutic effects throughout the entire pathological process from onset and progression to resolution.

References:

[1] CDE Official Website

[2] Insight Database

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