Study: Iptacopan superior to placebo in reducing proteinuria at 9 months
Key takeaways:
- Patients treated with iptacopan had a 38.3% reduction in proteinuria at 9 months.
- Iptacopan was well-tolerated and had a favorable safety profile.
LONG BEACH, Calif. — Iptacopan may be superior to placebo in reducing proteinuria at 9 months, with early onset and effect consistency, according to data presented at the National Kidney Foundation Spring Clinical Meetings, here.
“In immunoglobulin A neuropathy [IgAN], part of the immune system called the alternative complement pathway can become overly activated in the kidneys, which causes an inflammatory response, leading to progressive kidney damage and gradual loss of kidney function. The loss of kidney function, together with potential side effects of IgAN treatments available until recently, significantly impact patients’ lives,” study investigator Dana V. Rizk, MD, of the University of Alabama at Birmingham, said in a press release.
Researchers studied 250 patients for an efficacy analysis and 443 patients to analyze safety of iptacopan (fabhalta, Novartis) in a pre-specified interim analysis. The APPLAUSE-IgAN study enrolled patients with an eGFR of at least 30 mL/min/1.73 m2 and a urine albumin-to-creatinine ratio of at least 1 g/g based on a 24-hour urine collection at baseline, as well as a smaller cohort with severe renal impairment, defined as an eGFR between 20 mL/min/1.73 m2 and 30 mL/min/1.73 m2 at baseline.
The goal of the interim analysis was to study iptacopan in addition to optimized supportive care in patients with biopsy-confirmed immunoglobulin A neuropathy (IgAN) and proteinuria, despite having maximally tolerated renin-angiotensin system inhibition for at least 3 months. Patients were randomized 1:1 to either 200 mg of iptacopan or placebo twice daily. The main outcome was the ability of iptacopan to slow IgAN by measuring the annualized total eGFR slope for 24 months. Results are expected post-completion in 2025.
Baseline characteristics were balanced across treatment groups. Findings showed patients treated with iptacopan in addition to standard supportive care had a 38.3% reduction in proteinuria at 9 months, as measured by the 24-hour urine protein-to-creatinine ratio.
Urine protein-to-creatinine ratio from first morning void decreased as early as week 2 and continued to decrease during 9 months. About twice as many patients on iptacopan reached a 24-hour urine protein-to-creatinine ratio below 1 g/g at month 9.
Additionally, iptacopan was well-tolerated and had a favorable safety profile.
“Fabhalta is the first potential treatment for IgAN that specifically targets the alternative complement pathway,” Rizk said.
Iptacopan received FDA approval in 2023 for the treatment of nocturnal hemoglobinuria.
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Rizk DV, et al. Paper 448. Presented at: NKF Spring Clinical Meetings; May 14-18, 2024; Long Beach, Calif.