Treatment with telitacicept led to a significant reduction in proteinuria among patients with immunoglobulin A nephropathy (IgAN) compared with placebo, according to a phase III study presented at ASN Kidney Week 2025.

The primary endpoint of reducing proteinuria was met, with telitacicept demonstrating a 55-percent reduction in 24-hour urine protein-to-creatinine ratio (UPCR) at 39 weeks compared with placebo (p<0.0001), said lead author Dr Jicheng Lv from Peking University First Hospital in Beijing, China.

This phase III, multicentre, double-blind, placebo-controlled, two-part study (stages A and B) included 318 patients with biopsy-confirmed IgAN who were at high risk of progression, defined as 24-hour UPCR ≥0.8 g/g or total proteinuria ≥1.0 g/day, despite receiving stable therapy.

In the stage A part of the study, participants were randomly assigned to receive subcutaneous telitacicept 240 mg once weekly or a matching placebo (n=159 in each group) for 39 weeks. [ASN Kidney Week 2025, abstract SA-OR083]

At week 39, patients treated with telitacicept achieved a significantly greater reduction in 24-hour UPCR from baseline than those treated with placebo (-58.9 percent vs -8.8 percent).

Moreover, in a post hoc analysis, results showed that a higher percentage of patients in the telitacicept group achieved 24-hour UPCR thresholds of <0.5 g/g (42.1 percent vs 7.5 percent) and <0.3 g/g (24.5 percent vs 0.6 percent) than those in the placebo group.

The secondary endpoints of the study demonstrated additional benefits of telitacicept treatment. From baseline to week 39, the mean estimated glomerular filtration rate (eGFR) increased by 1.2 mL/min/1.73 m² in the telitacicept group, while a decrease of 3.7 mL/min/1.73 m² was noted in the placebo group.

Additionally, fewer patients treated with telitacicept experienced a ≥30 percent decline in eGFR at week 39 than those treated with placebo (6.3 percent vs 27 percent).

Among patients with haematuria at baseline, telitacicept therapy was associated with reduced prevalence of haematuria from 71.1 percent to 20.9 percent, whereas it increased from 71.3 percent to 73.5 percent with placebo. Of note, nearly 80 percent of telitacicept recipients achieved resolution of haematuria after 9 months of treatment, said Lv.

In terms of safety, treatment-emergent adverse events (TEAEs) occurred at a slightly higher rate with telitacicept than with placebo (89 percent vs 78.6 percent), but the incidence of serious TEAEs was lower with telitacicept (2.5 percent vs 8.2 percent).

Telitacicept was associated with more injection site reactions than placebo (50.3 percent vs 13.8 percent), but all were considered mild or moderate in severity.

Overall, after 9 months, telitacicept therapy demonstrated a rapid, substantial, and statistically significant reduction in proteinuria, and stabilized kidney function, with a favourable safety profile in patients with IgAN at high risk of progression, according to Lv.