Promising New IgAN Therapy Unveiled at 2024 Kidney Foundation Spring Meetings

In NEW YORK on May 14, 2024, during a late-breaking abstract presentation at the 2024 NKF Spring Clinical Meetings (SCM), Dr. Dana Rizk from the University of Alabama at Birmingham (UAB) Medical Center will reveal new data on the effects and safety of Fabhalta (iptacopan) for treating patients with IgA nephropathy (IgAN), also known as Berger disease. Initially approved by the FDA in 2023 for paroxysmal nocturnal hemoglobinuria, iptacopan is now showing promise for IgAN, a glomerular disease that can lead to chronic kidney disease (CKD) and is a leading cause of end-stage renal disease (ESRD).

The presentation, titled "Efficacy and Safety of Iptacopan in Patients with IgAN: Interim Analysis (IA) of the Phase 3 APPLAUSE-IgAN Study," will take place at the Long Beach Convention Center on May 15 from 2:30 to 4:30 p.m. (PT). The study's interim analysis indicates that patients receiving iptacopan along with standard supportive care experienced a 38.3% reduction in proteinuria after nine months, as measured by the 24-hour urine protein to creatinine ratio (UPCR), compared to a placebo. Proteinuria reduction is an important marker for kidney function decline, often used in IgAN clinical trials to support faster regulatory approvals.

The APPLAUSE-IgAN study is the first Phase III multicenter, randomized, placebo-controlled investigation to demonstrate significant proteinuria reduction by targeting the complement system in IgAN patients. This interim analysis included 250 patients for efficacy and 443 for safety analysis. Dr. Rizk, a member of the APPLAUSE-IgAN Steering Committee, described Fabhalta as the first potential treatment for IgAN that specifically targets the alternative complement pathway, reducing inflammatory responses that lead to kidney damage.

The APPLAUSE-IgAN study will continue in a double-blind format until the final analysis, which will evaluate iptacopan's ability to slow IgAN progression by measuring the estimated glomerular filtration rate (eGFR) slope over 24 months, with final results expected in 2025. The primary endpoints include proteinuria reduction at nine months and the annualized total eGFR slope over 24 months. Secondary endpoints will assess the proportion of participants achieving a UPCR of less than 1 g/g without needing corticosteroids or other immunosuppressants, the time to kidney failure events, and changes in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire.

The main study cohort included patients with an eGFR of at least 30 mL/min/1.73 m2 and a UPCR of at least 1 g/g at baseline. There was also a smaller cohort with severe renal impairment to provide additional data without contributing to the main efficacy analyses.

Dr. Sylvia Rosas, President of the NKF, emphasized the importance of the APPLAUSE-IgAN study, noting that it offers promising insights for healthcare providers and patients with IgAN. The study underscores the potential of targeting the alternative complement pathway to slow the progression of chronic kidney disease and avoid kidney failure.

The 2024 NKF Spring Clinical Meetings, held from May 14-18 in Long Beach, CA, provide a platform for nephrology professionals to learn about the latest developments, network with peers, and present research findings. This conference aims to translate scientific advancements into practical applications for improving patient health outcomes.

In the United States, over 37 million adults are estimated to have chronic kidney disease, with about 90% unaware of their condition. Risk factors include diabetes, high blood pressure, heart disease, obesity, and a family history of kidney disease. Certain ethnic groups, including Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, and Native Hawaiian or Other Pacific Islander, are at higher risk for developing kidney disease.

Healthcare professionals can join the National Kidney Foundation (NKF) to access resources, professional education discounts, and a network of colleagues dedicated to treating kidney disease. The NKF aims to promote meaningful changes in healthcare practices to improve the lives of those affected by kidney conditions.