Iptacopan both safe and effective for decreasing proteinuria in patients with immunoglobulin A nephropathy: APPLAUSE-IgAN trial
Presenter: Dana V. Risk, MD, University of Alabama at Birmingham, Birmingham, AL
Iptacopan decreased proteinuria by 35% in patients with immunoglobulin A nephropathy and low estimated glomerular filtration rates, making it a potential treatment option for these patients.
In patients with immunoglobulin A nephropathy (IgAN) and low estimated glomerular filtration rates (eGFR), iptacopan decreased proteinuria by nearly 35% versus placebo after 9 months of therapy and had a favorable side effect profile, according to a subgroup analysis of the phase 3 APPLAUSE-IgAN trial presented by Dana V. Rizk, MD, University of Alabama at Birmingham, Birmingham, AL. Currently, treatment of patients with advanced IgAN and low eGFR (<30 mL/min/1.73 m2) is limited to supportive care, she stated in a Kidney Week 2024 poster presentation. Thus, iptacopan may be a treatment option for this patient population.
Iptacopan (FABHALTA), approved for treatment of paroxysmal nocturnal hemoglobinuria and primary IgAN by the US Food and Drug Administration in 2023, specifically binds complement Factor B and inhibits the alternative complement pathway involved in IgAN pathogenesis.
The randomized, double-blind, placebo-controlled APPLAUSE-IgAN trial enrolled adults with biopsy-confirmed IgAN and proteinuria of at least 1 g/g (gram of protein per gram of creatinine in the urine) despite stable supportive therapy. Patients were randomized 1:1 to iptacopan 200 mg or placebo twice daily for 24 months while remaining on supportive therapy.
Dr. Rizk presented results from subcohort of 27 patients (13 iptacopan, 14 placebo) from the APPLAUSE-IgAN study with baseline eGFR levels of 20 to under 30 mL/min/1.73 m2. Baseline demographic and disease characteristics were similar for both the iptacopan and placebo groups. Baseline median 24-hour urine protein-creatinine ratios (UPCR) were 2.1 g/g (range 1.7-2.5 g/g) for the iptacopan arm and 1.8 g/g (1.4-2.4 g/g) in the placebo arm. The mean eGFRs were 24.7 and 25.8 mL/min/1.73 m2, respectively. All patients had received maximally approved and tolerated renin-angiotensin system inhibitor doses. Safety, efficacy, and pharmacokinetic data for this cohort were assessed at the month 9 interim analysis.
The most frequent adverse event, Dr. Rizk reported, was COVID-19 (23.1% iptacopan; 35.7% placebo). Two patients in each trial arm had serious adverse events and 1 in each arm discontinued treatment because of adverse events.
Results showed that proteinuria decreased by 28% from baseline (UPCR 2.07 g/g [range 1.68-2.54 g/g]) to month 9 (1.49 g/g [1.16-2.24]) in the iptacopan arm but increased by 10% in the placebo arm from 1.78 g/g (1.40-2.17) to 2.06 g/g (1.39-3.38) at month 9. Results for the 24-hour UACR were similar showing a 27% decrease for iptacopan from a baseline of 1.66 g/g (1.26-2.08) to 1.17 g/g (0.9-1.60) at month 9 versus 1.57 g/g (1.09-1.80) to 1.71 g/g (1.05-2.50) for placebo. At month 9, the relative reduction in median 24-hr UPCR was 34.5% for iptacopan versus placebo, consistent with the primary analysis.
Dr. Rizk concluded, “In patients with baseline eGFR 20 to less than 30 mL/min/1.73m2, iptacopan was well tolerated with a favorable safety profile and decreased proteinuria versus placebo by 34.5% at month 9. Iptacopan may therefore represent a potential treatment option for patients with low eGFR.”
Funding
- Commercial Support – Novartis Pharma AG