Iptacopan Maintains Kidney Benefit Through 48 Months in IgA Nephropathy

Iptacopan (Fabhalta), an oral complement factor B inhibitor, continued to slow kidney function decline and sustain proteinuria reductions for up to 48 months in adults with IgA nephropathy, according to data from the ongoing open-label rollover extension program (REP) of the phase 3 APPLAUSE-IgAN trial. Patients switching from placebo to iptacopan in the REP saw their annualized eGFR slope improve from −5.29 to −2.11 mL/min/1.73 m² per year.1

Brad Rovin, MD, of The Ohio State University Wexner Medical Center, and colleagues presented the findings at ASN Kidney Week 2026 in Denver, Colorado.1

At the 24-month final analysis of APPLAUSE-IgAN, iptacopan slowed eGFR decline versus placebo by 3.02 mL/min/1.73 m² per year, supporting full US Food and Drug Administration approval for adults with primary IgA nephropathy at risk of disease progression.2,3 Investigators noted longer-term evidence was still needed to confirm a sustained effect. The REP was designed to evaluate long-term safety and tolerability, with efficacy as a secondary objective.1

How Did Iptacopan Affect Long-Term eGFR Slope in APPLAUSE-IgAN?

Patients completing APPLAUSE-IgAN or the phase 2 iptacopan trial could enroll in the REP and receive iptacopan 200 mg twice daily alongside supportive care. Efficacy was analyzed in 368 APPLAUSE-IgAN participants entering the REP, including 194 originally randomized to iptacopan and 174 originally randomized to placebo. At baseline, 99.5% were receiving an ACE inhibitor or ARB and 20.7% were receiving an SGLT2 inhibitor.1

Among patients treated with iptacopan for up to 48 months, the annualized total eGFR slope was −3.49 mL/min/1.73 m² per year (95% CI, −4.17 to −2.80).¹ This compared with −3.10 mL/min/1.73 m² per year (95% CI, −3.80 to −2.40) over the first 24 months in APPLAUSE-IgAN.

In patients entering from the placebo arm, the eGFR slope was −5.29 mL/min/1.73 m² per year (95% CI, −6.09 to −4.49) during the 24-month double-blind period. After switching to iptacopan, the slope improved to −2.11 mL/min/1.73 m² per year (95% CI, −3.08 to −1.13) over the next 24 months.1

Were Proteinuria and Safety Outcomes Maintained With Long-Term Iptacopan?

In patients on iptacopan from the start of APPLAUSE-IgAN, the early reduction in first morning void urine protein-to-creatinine ratio (UPCR-FMV) persisted through 48 months (adjusted geometric mean ratio [GMR] to baseline, 0.61; 95% CI, 0.50–0.75).¹ Among those switching from placebo, UPCR-FMV remained near baseline at month 24 (GMR, 0.87; 95% CI, 0.79–0.96). After 24 months of iptacopan in the REP, UPCR-FMV fell to levels similar to those in the original iptacopan arm (GMR at month 48, 0.74; 95% CI, 0.59–0.91).1

The number of patients with hematuria also declined with continued iptacopan exposure in both groups, according to the investigators. The safety analysis included 489 patients, including 77 from the phase 2 trial, with a median treatment duration of 29.9 months and a maximum of 62.4 months.1

Treatment-emergent adverse events (TEAEs) occurred in 86.5% (423/489) of patients, and TEAEs led to iptacopan discontinuation in 4.3% (21/489). Serious TEAEs occurred in 17.4%, and serious or severe infections occurred in 8.0%. A total of 4 patients (0.8%) had confirmed infections with Streptococcus pneumoniae, all treated with antibiotics and recovered; study treatment was discontinued in each case.1

One death from acute pancreatitis occurred in the REP and was deemed unrelated to iptacopan.1 The authors concluded the long-term data support the established safety profile of complement inhibition with iptacopan.

The REP remains ongoing, and further long-term efficacy, safety, and tolerability data are expected.1 Iptacopan joins a growing set of IgA nephropathy therapies targeting distinct immunologic pathways, including APRIL and BAFF/APRIL inhibitors with phase 3 data presented at the same meeting.

References

1. Rovin B, Trimarchi H, Maes BD, et al. Long-term efficacy and safety of iptacopan in patients with IgA nephropathy. Poster presented at: ASN Kidney Week 2026; October 21-25, 2026; Denver, CO. Poster TH-PO1252. doi:10.1681/ASN.2026g3gjrew2

2. Barratt J, Rovin BH, Zhang H, et al. Efficacy and safety of iptacopan in IgA nephropathy. N Engl J Med. 2026;395:465-477.

3. Fabhalta (iptacopan) capsules, for oral use. Prescribing information. Novartis Pharmaceuticals Corporation; 2025. Accessed October 22, 2026. https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf