From November 5 to 9, local time, the 58th American Society of Nephrology (ASN) Kidney Week 2025 was held in Houston, Texas. As a premier global academic event in the field of nephrology, this conference unveiled several significant research advancements in the treatment of IgA nephropathy (IgAN). This article provides an overview of the cutting-edge developments and trends in IgAN treatment from multiple perspectives, including small nucleic acid drugs, antibody therapies, and small molecule drugs.
01 Small Nucleic Acid Drugs
In the small nucleic acid drug space, domestic innovative pharmaceutical companies have demonstrated strong R&D capabilities.
At this year's conference, Frontage Biotech presented comprehensive preclinical efficacy data for two of its independently developed small nucleic acid drugs: the single-target FB7013, which targets MASP-2, in a cynomolgus monkey model of IgAN, and the latest preclinical efficacy data for the dual-target FB7011 in the same model.
FB7013: The First siRNA Drug Targeting MASP-2
FB7013 is currently the first siRNA drug targeting MASP-2, a key factor in the lectin pathway, and holds promise as a novel mechanism-based therapeutic option for IgAN and other complement-mediated diseases. Data presented at the conference showed that FB7013 achieved over 90% suppression of MASP2 mRNA in vitro, with a half-maximal inhibitory concentration (IC50) in the picomolar range. In a humanized MASP2 transgenic mouse model, a single dose resulted in sustained silencing of liver MASP2 mRNA for up to two months. In cynomolgus monkeys, FB7013 achieved MASP2 protein expression suppression for up to four months, with statistically significant effects.
These results indicate that FB7013 provides potent and durable inhibition of lectin pathway activation. From a pharmacodynamic perspective, the drug may support a dosing regimen of once every six months in humans, potentially addressing current challenges related to both efficacy and dosing frequency.
FB7011: Dual-Target Synergy for "Dual-Pathway Interception"
FB7011 innovatively targets both the lectin pathway (MASP-2) and the alternative pathway (CFB), a "dual-pathway interception" design not previously reported in existing small molecules or monoclonal antibody drugs. Given that complement activation in IgAN often involves both the lectin and alternative pathways, FB7011 demonstrates unique mechanistic advantages.
Preclinical data showed that FB7011 inhibited both MASP2 and CFB mRNA by over 90% in vitro, with IC50 values in the picomolar range. In double-transgenic mice and cynomolgus monkey models, a single dose effectively silenced both CFB and MASP2 mRNA while inhibiting MASP2 protein expression. No off-target effects or immunotoxicity were observed in vitro, and FB7011 exhibited good tolerability in vivo. Its pharmacodynamic profile may support a twice-yearly dosing regimen in humans.
Both FB7011 and FB7013 are small nucleic acid drugs targeting the complement system, featuring innovative mechanisms of action. They hold the potential to significantly enhance the efficacy and safety of IgAN treatment and improve patient medication adherence. Beyond IgAN, these two drugs could also be expanded to treat other diseases caused by abnormal complement activation in the long term - including primary membranous nephropathy (PMN), age-related macular degeneration/geographic atrophy (AMD/GA), and diabetic kidney disease (DKD) - offering new therapeutic options for a broader patient population.
SGB-9768 by Sylentis: An RNAi Therapy Targeting C3
Sylentis, a company focused on RNAi drug development, presented two Phase I clinical study data sets for its RNAi therapy SGB-9768, which targets complement C3, in poster format. SGB-9768 is the first siRNA drug in China targeting complement C3, utilizing the company's proprietary GalNAc liver-targeted delivery technology to specifically inhibit C3 expression via RNAi, thereby suppressing excessive complement system activation at its source.
Phase I clinical trial results showed that a single subcutaneous injection of SGB-9768 exhibited good safety and tolerability, along with dose-dependent, significant, and sustained reductions in C3 protein levels and inhibition of complement pathway activity. Compared to other siRNA products targeting the same pathway, SGB-9768 achieved higher target protein knockdown levels at the same dose and maintained longer drug efficacy duration, demonstrating potential as a "best-in-class" candidate. With its notable long-acting properties, SGB-9768 may enable dosing intervals of every three or six months, greatly improving patient convenience. The drug has now entered Phase II clinical trials in China and has been granted orphan drug designation by the U.S. FDA for the treatment of C3 glomerulopathy.
02 Antibodies / Fusion Proteins
Telitacicept: A BLyS/APRIL Dual-Target Fusion Protein
Telitacicept, a BLyS/APRIL dual-target fusion protein developed by RemeGen, had its Phase III clinical trial data for the treatment of IgA nephropathy (IgAN) in China presented at this year's ASN Kidney Week as a "Late-Breaking Oral Presentation."
Previously, in August 2025, RemeGen announced that the A-phase of this study had met its primary endpoint: compared to the placebo group, patients treated with telitacicept achieved a 55% reduction in the 24-hour urine protein-to-creatinine ratio (UPCR) over a 39-week treatment period (P < 0.0001), with a favorable safety and tolerability profile. Detailed data from this study were unveiled at the ASN meeting.
Based on these positive results, the marketing application for telitacicept in the treatment of primary IgAN has been accepted by the Center for Drug Evaluation (CDE) in China and granted priority review status, paving the way for earlier access for Chinese patients.
The Chinese Clinical Practice Guideline for Adult IgA Nephropathy and IgA Vasculitis Nephritis (2025), released in October 2025, included telitacicept for the first time as a BLyS/APRIL dual-target fusion protein. By effectively inhibiting B-cell activation and IgA production, the drug has demonstrated promising efficacy in Phase II trials and multiple real-world studies. The guideline recommends considering telitacicept as a new treatment option for Chinese IgAN patients who remain at high risk of progression or exhibit refractory disease despite adequate supportive therapy and conventional immunosuppressive treatment.
Zigakibart: A Monoclonal Antibody Targeting APRIL
Zigakibart is a novel humanized monoclonal antibody that works by binding to and blocking a proliferation-inducing ligand (APRIL). By doing so, it reduces pathogenic galactose-deficient IgA1 (Gd-IgA1) levels and blocks the formation of pathogenic immune complexes, thereby intervening in the disease progression of IgAN.
At the ASN meeting, subgroup analysis results from the Phase I/II ADU-CL-19 study of Zigakibart were presented. This analysis included 35 patients from the biomarker analysis set who had data available at week 100, aiming to evaluate long-term renal function changes across different subgroups based on baseline eGFR and UPCR levels.
The results showed that patients stratified by baseline eGFR maintained stable eGFR levels throughout the 100-week treatment period with Zigakibart. Similarly, patients grouped by baseline UPCR also exhibited a consistent trend of eGFR stability over the 100-week treatment course. These findings suggest that the efficacy of Zigakibart is independent of disease severity and that it can effectively protect renal function regardless of patients' baseline eGFR and UPCR levels.
03 Small Molecule Drugs
Small molecule drugs, with their well-established administration methods and clear clinical value, play a pivotal role in the treatment of IgA nephropathy (IgAN).
Nefecon: The World's First Disease-Modifying Treatment for IgAN
Budesonide delayed-release capsules (brand name: Nefecon) are the world's first disease-modifying therapeutic agent for IgAN, functioning as an immunomodulator that targets B cells in the intestinal mucosa. At this year's ASN meeting, seven new studies on Nefecon were presented, exploring its efficacy and safety in treating IgAN from multiple dimensions.
The findings demonstrated that Nefecon offers significant clinical value in three key aspects: disease-modifying therapy, early intervention, and long-term treatment. Real-world studies confirmed that Nefecon exhibits good efficacy and safety in clinical practice. Early intervention plays a crucial role in reducing proteinuria and stabilizing renal function. Additionally, extended treatment data beyond nine months provided strong evidence supporting its long-term efficacy and safety.
Thanks to its innovative mechanism and clinical advantages, Nefecon has been included in both the 2025 KDIGO Clinical Practice Guideline for the Management of IgA Nephropathy and IgA Vasculitisand the Chinese Clinical Practice Guideline for Adult IgA Nephropathy and IgA Vasculitis (2025). It is currently the only disease-modifying treatment for IgAN recommended by both international and domestic guidelines, further solidifying its foundational role in first-line therapy.
Iptacopan: Precision Inhibition of the Complement Alternative Pathway
Developed by Novartis, iptacopan is the first-in-class inhibitor of complement factor B (CFB), targeting the alternative complement pathway. It was approved by China's National Medical Products Administration (NMPA) in September 2025 for the treatment of primary IgAN.
At the ASN meeting, interim results from the APPLAUSE-IgAN Phase III clinical trial in East Asian patients were presented. The study included 102 East Asian patients in the efficacy analysis and 177 in the safety analysis. Results showed that, compared to placebo, the iptacopan group achieved a 38.0% reduction in 24-hour UPCR from baseline at 9 months, and a 36.5% reduction in first-morning void (FMV) and urine protein-to-creatinine ratio (UPCR-FMV).
In terms of safety, the incidence of treatment-related adverse events was similar between the iptacopan and placebo groups. The iptacopan group had a drug discontinuation rate due to adverse events of 1.1%, compared to 2.2% in the placebo group, indicating that iptacopan is well tolerated and has a favorable safety profile.
04 Conclusion
IgA nephropathy (IgAN), as the most common primary glomerulonephritis worldwide, affects a large patient population and carries a high risk of disease progression. According to statistics, the global number of IgAN patients is projected to exceed 10.2 million by 2030, with approximately 4.59 million adult patients in China-over 100,000 new cases annually, 80% of whom are young and middle-aged individuals aged 20–59. More alarmingly, over half of diagnosed patients may progress to end-stage renal disease (ESRD) within 20 years, necessitating life-long dependence on dialysis or kidney transplantation. The cost of dialysis in the first year alone can reach 120,000 to 200,000 RMB, placing a heavy burden on both families and society.
According to a report by Frost & Sullivan, the global market size for IgA nephropathy therapeutics is expected to grow from 567millionin2020to1.196 billion in 2025, representing a compound annual growth rate (CAGR) of 16.1%. In China, the market size is projected to rise from 37millionin2020to109 million in 2025, and is further expected to expand to $507 million by 2030.
The numerous research findings presented at this year's ASN Kidney Week not only achieved breakthroughs in efficacy but also continued to optimize treatment in terms of dosing frequency, safety, and suitability for diverse patient populations, offering patients higher-quality therapeutic options. As these innovative drugs advance through clinical trials and become commercially available, they hold the potential to alleviate the medical and financial burdens on patients and society, bringing new hope to IgA nephropathy patients worldwide.
References:
1.Official websites of respective companies
2.ASN official website
3.Open Source Securities
