Yesterday (June 4), the official website of the National Medical Products Administration (NMPA) showed that Otsuka Pharmaceutical's application for Sibeprenlimab injection was conditionally approved for marketing, for the treatment of adult patients with primary immunoglobulin A nephropathy (IgAN) to maintain their kidney function. This application had previously been included in the priority review list.
Sbelimab is the world's first approved monoclonal antibody drug targeting the inhibition of proliferation-inducing ligand (APRIL) . Its approval in China marks a new stage in the treatment of IgA nephropathy in China, moving from traditional supportive care to precise intervention targeting upstream causes.

01

IgA nephropathy is highly prevalent and difficult to treat.
IgA nephropathy is the most common primary glomerular disease in China, with a patient population of over 2.2 million. The disease is concentrated in young adults aged 16 to 40 and is the leading cause of progression to end-stage renal disease (uremia) in young and middle-aged adults.

The disease is caused by the formation of immune complexes by pathogenic galactose-deficient IgA1 ( Gd-IgA1 ), which damage the kidneys. Most patients experience progressive decline in kidney function within ten years of diagnosis.

Currently, mainstream clinical treatments primarily rely on symptomatic medications such as ACEIs/ARBs and SGLT2 inhibitors, which can only delay symptoms and cannot block the generation of pathological antibodies at the source of the disease. Hormones and traditional immunosuppressants have significant side effects, and their long-term safety is limited. A large number of patients with high proteinuria and high risk of disease progression lack targeted drugs, resulting in a huge unmet clinical need.

02

Mechanism of action of sbelimumab
Spelelimab is a humanized IgG2 monoclonal antibody that binds to and inhibits the activity of APRIL with high affinity and high specificity . By neutralizing APRIL , this drug can reduce the generation of pathogenic Gd-IgA1 at the source of the disease , thereby blocking the deposition of immune complexes in the glomerular mesangial area and delaying the progression of glomerular damage and fibrosis.

Unlike traditional drugs that primarily target downstream inflammatory or fibrotic pathways, sbelimumab provides a systemic intervention against upstream disease drivers. Furthermore, its four-week subcutaneous injection regimen allows patients to self-administer the medication at home after training, potentially significantly improving long-term treatment adherence.

03

Clinical trial data
The efficacy and safety of sbelizumab have been validated by multiple rigorous clinical trials. Among them, the global pivotal Phase III VISIONARY study was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 510 adult patients with IgA nephropathy who were receiving standard supportive care (including the maximum tolerated dose of a RAS inhibitor, which could be combined with an SGLT2 inhibitor) to evaluate the efficacy and safety of subcutaneous injections of 400 mg sbelizumab every four weeks .

Interim analysis of the study ( n=320 ) showed that at 9 months of treatment, the 24- hour urinary protein-to-creatinine ratio ( uPCR ) in the sbelimab group decreased by an average of 50% from baseline, while it increased by 2% in the placebo group . After placebo correction, sbelimab reduced proteinuria levels by a relative 51% .

Reduced proteinuria is a recognized surrogate endpoint for delaying the progression of kidney failure, and this positive result provided key evidence for its previous accelerated approval by the US FDA ( Monthly! World's first IgA nephropathy drug approved by the FDA ) . The study is ongoing, and secondary endpoint data on the 24 -month annualized slope of eGFR are expected to be available this year to further clarify its long-term protective benefit on kidney function.

Of particular note is the data from the Chinese subgroup of the VISIONARY study, presented for the first time at the World Congress of Nephrology ( WCN 2026 ), which provides direct evidence-based support for the use of this drug in Chinese patients. This subgroup included 42 Chinese patients ( 25 in the sbelimab group and 17 in the placebo group ). After 9 months of treatment, the uPCR-24h in the sbelimab group was significantly reduced by 63.1% from baseline ( 95% CI 52.1%-71.6% ), while the placebo group only saw a 3.1% reduction . The adjusted relative reduction in proteinuria in the treatment group reached 61.9% , an improvement even superior to that seen in the global population. Meanwhile, sbelimumab can rapidly and sustainably reduce serum IgA ( -62.0% ), Gd-IgA1 ( -65.6% ), and APRIL ( -95.8% ) levels. Compared with the placebo group, more patients achieved clinical remission of proteinuria at 12 months, and the rate of hematuria resolution was higher at week 48 .

Regarding safety, sbelimumab demonstrated good tolerability in both the global population and the Chinese subgroup. Data from the Chinese subgroup showed that the incidence of treatment-specific adverse events ( TEAEs ) was comparable between the sbelimumab and placebo groups; no drug-related serious adverse events leading to treatment discontinuation or deaths were reported. In the global study, the incidence of TEAEs in the sbelimumab and placebo groups was 76.3% and 84.5% , respectively , with serious TEAEs occurring in 3.9% and 5.4% of patients, respectively . The overall safety profile was consistent with previous data, and no new safety signals were identified.

04

Competitive landscape in the same track
Currently, five drugs are approved globally for the treatment of IgA nephropathy. Besides sipelimab, the other four are: budesonide , which targets intestinal mucosal B cells ; sparsentan , an endothelin / angiotensin dual receptor antagonist ; iprocoman , a complement factor B inhibitor ; and atrasentan, a selective endothelin A receptor antagonist . These four are all small-molecule chemical drugs, and their mechanisms of action are primarily focused on downstream inflammatory or fibrotic pathways, or they exert their effects through local immune modulation.

Speleximab is the only large-molecule monoclonal antibody among them, which systematically neutralizes APRIL to reduce the production of pathogenic IgA at its source , representing a revolutionary mechanism. Furthermore, its subcutaneous injection regimen once every four weeks offers advantages in convenience and adherence compared to daily oral chemotherapy or regimens requiring frequent dosing.

In addition to the approved products, there are other similar biologics in China, such as Telitacicept, Povetacicept (co-developed with Zai Lab), and acecept, which are in the application for marketing approval or late-stage clinical trials. In the future, competition in this field will revolve around long-term renal function protection data, ease of administration, and combination therapy strategies.

Conclusion

The launch of sbelimumab in China not only provides patients with IgA nephropathy with a new and effective treatment, but also further validates the core value of targeting the APRIL pathway in the treatment of this disease. Its long-term benefits, especially its ability to slow the rate of decline in glomerular filtration rate, will be revealed upon the completion of the VISIONARY study, which will be key evidence for establishing its status as a first-line or combination therapy.
For many patients, the advent of sbelimumab means another powerful safeguard in their lives, helping them delay kidney failure and avoid dialysis. This advancement undoubtedly marks a significant step forward in the precision and long-term effectiveness of chronic kidney disease management in my country.

https://mp.weixin.qq.com/s/csvMIfy8tgYtHGsifxxHjw