Novartis presented new data of Fabhalta showing improvement in proteinuria in patients with IgA nephropathy
Novartis revealed new data today on Fabhalta (iptacopan), showcasing a significant reduction in proteinuria compared to placebo for patients with IgA nephropathy (IgAN). This marks a crucial milestone as APPLAUSE-IgAN becomes the first Phase III study to demonstrate such a reduction by targeting the complement system in IgAN patients.
IgAN stands as a complex and rare kidney disease, posing a significant threat to global kidney health. Complement activation plays a pivotal role in igniting glomerular inflammation in IgAN, emphasizing the urgency for effective, targeted therapies.
The interim analysis of the Phase III APPLAUSE-IgAN study unveiled promising outcomes for Fabhalta® (iptacopan), an investigational Factor B inhibitor of the alternative complement pathway. Patients treated with Fabhalta exhibited a notable 38.3% reduction in proteinuria at the nine-month mark, compared to placebo alongside supportive care.
Proteinuria reduction emerges as a vital surrogate marker, closely linked to the progression towards kidney failure. It serves as a critical endpoint in IgAN clinical trials, potentially paving the way for accelerated approvals. Importantly, Fabhalta demonstrated a favorable safety profile consistent with previous data, ensuring patient well-being throughout the study.
The APPLAUSE-IgAN study, a Phase III multicenter endeavor, is underway in a double-blind fashion, with a primary focus on evaluating Fabhalta's ability to slow IgAN progression. Submission for possible accelerated approval to the FDA has been accepted, with priority review granted. The study's primary endpoint, evaluating Fabhalta's effect on the annualized total estimated glomerular filtration rate (eGFR) slope over 24 months, is anticipated upon study completion in 2025.
The study, registered as NCT04578834, encompasses 518 adult primary IgAN patients. Key endpoints include proteinuria reduction at nine months and the annualized total eGFR slope over 24 months. Secondary endpoints will assess various factors, including fatigue scale measurements and the proportion of participants reaching specific kidney failure endpoint events.
The main study population comprises patients with baseline eGFR ≥30 mL/min/1.73 m2 and UPCR ≥1 g/g. Additionally, a smaller cohort with severe renal impairment at baseline will provide supplementary insights but won't factor into the primary efficacy analyses.