Treatment with telitacicept significantly reduced proteinuria in patients with immunoglobulin A (IgA) nephropathy compared with placebo, according to data from a phase 3 study involving more than 300 patients.

IgA nephropathy, a chronic autoimmune kidney disease, remains a leading cause of kidney failure, wrote Jicheng Lv, MD, of the Renal Division at Peking University First Hospital in Beijing, China, and colleagues.

Historically, effective and well-tolerated therapies for IgA nephropathy have been limited, said David Charytan, MD, MSc, director of the Division of Nephrology at NYU Langone Health, New York City, who was not involved in the study.

“However, there has been a veritable explosion of new therapies in the last 2-3 years,” Charytan said.

Telitacicept is among the latest therapies targeting pathways implicated in IgA nephropathy. The fusion protein targets both B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two pathways involved in disease pathogenesis.

Phase 3 Trial Results

Results from a previous phase 2 study showed reductions in galactose-deficient IgA1 levels. To determine whether those biologic effects translated into clinical benefit, investigators launched the phase 3 TELIGAN trial, the interim results of which were published in The New England Journal of Medicine.

Investigators randomized 318 adults with confirmed IgA nephropathy and persistent proteinuria (≥ 1.0 g/d) to receive subcutaneous telitacicept 240 mg or placebo once weekly. The trial is ongoing at 72 sites in China.

The primary endpoint was the change from baseline in the geometric mean 24-hour urinary protein-to-creatinine ratio at 39 weeks.

At week 39, the adjusted geometric mean ratios of the 24-hour urinary protein-to-creatinine ratios compared to baseline were 0.41 in the telitacicept group and 0.91 in the placebo group, corresponding to percentage changes of -58.9% and -8.8%, respectively. The between-group difference was significant at -55.0% (P < .001).

In addition, significantly fewer patients receiving telitacicept vs placebo experienced a decline in estimated glomerular filtration rate of at least 30% from baseline through week 39 (6.3% vs 27.0%).

The treatment effect was consistent across all prespecified subgroups. Telitacicept also appeared to reduce hematuria, although those findings were not conclusive.

Overall, treatment-related adverse events were more common with telitacicept than with placebo (77.4% vs 48.4%). The most common adverse event in both groups was upper respiratory tract infection, reported in 40.9% of the telitacicept group and 36.5% of the placebo group.

No serious treatment-related adverse events occurred in the telitacicept group, and one was reported in the placebo group. No deaths were reported in either group.

Injection-site reactions occurred in 50.3% of patients receiving telitacicept and 13.8% of those receiving placebo. Most reactions were mild.

The study was limited by its exclusively Asian population, which may limit generalizability, and the interim nature of the findings. Longer-term data will be evaluated at week 104, the researchers noted.

However, the interim results support telitacicept as a potential treatment option for patients with IgA nephropathy, they concluded.

Expanding Treatment Options

IgA nephropathy is associated with progressive chronic kidney disease and progression to end-stage kidney disease in approximately 20% of patients over 10-20 years, although the risk is higher among patients similar to those enrolled in the current study, Charytan said.

The findings were not surprising given the efficacy seen with other agents targeting the BAFF/APRIL pathways in recent years, he added. Povetacicept, sibeprenlimab, and atacicept have demonstrated promising results in recent clinical trials and share related mechanisms of action.

“I think these agents are likely to become the standard of care for this disease; they seem very well tolerated and very effective,” Charytan said.

Looking ahead, larger studies with long follow-up are needed to better define safety and determine whether these therapies induce durable remission and can eventually be discontinued or whether long-term treatment will be required, he said.

The study was supported by RemeGen. Disclosure information for the study authors is available in the original publication. Charytan disclosed serving as an expert witness in a patent case involving an agent unrelated to IgA nephropathy.