Iptacopan Slows Decline of Kidney Function in Patients With IgA Nephropathy

The complement factor B inhibitor iptacopan (Fabhalta; Novartis) significantly slows the decline of kidney function in patients with immunoglobulin A (IgA) nephropathy after 24 months when compared to placebo.

The new report, which was published in The New England Journal of Medicine, confirms the findings of a 9-month interim analysis.¹

The authors explained that the standard treatment for IgA nephropathy is lifestyle modification, blood-pressure control, and antiproteinuric agents. Still, about half of people diagnosed with IgA nephropathy will go on to develop kidney failure within 20 years of diagnosis, they noted.²

“However, a greater understanding of the pathophysiological features of IgA nephropathy has supported the development of therapies that target the underlying pathobiologic mechanism,” the authors wrote. They added that current guidelines suggest addressing IgA nephropathy-specific immunological factors and chronic kidney disease simultaneously, as both are fundamental drivers of nephron loss.

Scientists believe overactivation of the alternative complement pathway is a major mechanism by which IgA nephropathy contributes to glomerular inflammation and kidney injury. They noted that glomerular C3 deposition, in particular, is common among people with IgA nephropathy and has been linked with inferior outcomes.

The complement factor B inhibitor iptacopan is an oral therapy that targets complement factor B of the alternative pathway, the authors noted.

“Inhibition of factor B blocks alternative pathway-mediated C3 cleavage and activation of the amplification loop, which subsequently prevents downstream generation of the membrane attack complex,” the authors wrote.

Previously reported data examining the potential benefits of iptacopan in patients with IgA nephropathy—including the 9-month interim analysis of the current phase 3 trial—found it was effective at slowing the loss of kidney function in patients who were at high risk of rapid progression.³ The new data are the final results of that phase 3 trial, offering insights into the efficacy of the therapy at 24 months.

To qualify for the trial, patients needed to be at least 18 years of age and have an estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m² of body-surface area and have a 24-hour urinary protein-to-creatinine ratio of at least 1 despite supportive care. The trial was a double-blind trial in which 238 patients were assigned to receive a 200 mg oral dose of iptacopan twice daily, and 239 patients were assigned to receive a placebo twice daily. The primary endpoint was the annualized total eGFR slope as estimated over a 24-month period.

The data showed a significant difference in the rate of decline among people receiving the therapy. In the iptacopan group, the annualized total eGFR slope was –3.10 mL per minute per 1.73 m² per year. In the placebo group, the rate was –6.12 ml per minute per 1.73 m² per year, a difference of 3.02 ml per minute per 1.73 m² (95% CI, 2.02-4.01; adjusted P < .001). Using a composite endpoint, the investigators found that 21.4% of patients in the iptacopan group and 33.5% of patients in the placebo group experienced a kidney failure event (HR, 0.57; 95% CI, 0.40-0.81; adjusted P = .003).

Rates of adverse events and serious adverse events were similar in both groups, with serious adverse events occurring in approximately 12% of participants in both groups. Serious infections occurred in 6.7% of those in the iptacopan group, compared to 2.1% in the placebo group.

The authors noted that a number of questions about iptacopan remain unanswered, including how best to integrate the therapy into treatment sequences and what the longer-term benefits of its usage might be. They added that the current trial focused on patients at high-risk of progression, and thus it is not yet clear how it might impact patients at lower risk.

In the meantime, they said these data show iptacopan is a promising therapy that appears to have a significant impact on this patient group.

References:

1. Barratt J, Eren N, Kashihara N, et al. Iptacopan in IgA Nephropathy - Final 24-Month Data. N Engl J Med. Published online March 29, 2026. doi:10.1056/NEJMoa2600743

2. Pitcher D, Braddon F, Hendry B, et al. Long-Term Outcomes in IgA Nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727-738. doi:10.2215/CJN.0000000000000135

3. Perkovic V, Barratt J, Rovin B, et al. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N Engl J Med. 2025;392(6):531-543. doi:10.1056/NEJMoa2410316