Telitacicept Shows Significant Proteinuria Reduction in IgA Nephropathy Phase 3 Trial
China: A new interim analysis from a phase 3 clinical trial, published in The New England Journal of Medicine, suggests that telitacicept may offer a promising treatment option for patients with IgA nephropathy, a chronic kidney disease that can progress to kidney failure.
The study, led by Jicheng Lv from the Renal Division at Peking University First Hospital, Beijing, investigated the efficacy and safety of telitacicept in adults with biopsy-confirmed IgA nephropathy who continued to have significant proteinuria despite receiving standard supportive care.
IgA nephropathy is driven in part by immune system dysfunction involving B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), both of which contribute to disease progression. Telitacicept is a fusion protein designed to simultaneously inhibit BAFF and APRIL, thereby targeting key pathways involved in the disease process.
For this purpose, the researchers conducted a multicenter, double-blind, randomized, placebo-controlled phase 3 trial. A total of 318 patients were enrolled and randomly assigned in equal numbers to receive either weekly subcutaneous telitacicept at a dose of 240 mg or a matching placebo. All participants had persistent proteinuria of at least 1 gram per day at baseline despite appropriate background therapy.
The primary outcome was the change in the 24-hour urinary protein-to-creatinine ratio at 39 weeks compared with baseline. This marker is widely used to assess disease activity and progression risk in IgA nephropathy.
The findings were as follows:
- Telitacicept treatment led to a marked reduction in proteinuria, with a nearly 59% decrease in the urinary protein-to-creatinine ratio by week 39, compared with about 9% with placebo.
- This resulted in a significant relative improvement in proteinuria reduction in favor of telitacicept.
- Kidney function remained largely stable in the telitacicept group, with only a minimal decline in eGFR from baseline.
- Patients in the placebo group showed a greater decline in eGFR over the same period, indicating a possible protective effect of telitacicept on kidney function.
- Adverse events were more commonly reported in the telitacicept group than in the placebo group.
- Serious adverse events occurred less frequently in patients receiving telitacicept than in those receiving placebo.
- No new or unexpected safety concerns were identified during the study.
The findings indicate that telitacicept may significantly reduce proteinuria and help preserve kidney function in patients with IgA nephropathy who are at high risk of disease progression. These interim results support the therapeutic potential of targeting BAFF and APRIL pathways in this condition.
While the results are encouraging, longer follow-up and final trial data will be essential to confirm the durability of these benefits and further establish the safety profile of telitacicept.
Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2514415
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