Novartis Announces Positive Interim Results from Phase III APPLAUSE-IgAN Trial of Iptacopan, Demonstrating Significant Proteinuria Reduction in IgA Nephropathy Patients

Positive Key Results Achieved in Pre-specified Interim Analysis at Month 9 of the Phase III APPLAUSE-IgAN Study: Iptacopan Shows Superiority Over Placebo in Reducing Proteinuria in Patients with IgA Nephropathy.

Novartis Plans to Seek Accelerated Approval from the FDA in 2024 Based on Interim Data; Final Results (24 Months) of APPLAUSE-IgAN Study Expected in 2025.

Recently, Novartis announced positive topline results from the pre-specified interim analysis at 9 months of the Phase III APPLAUSE-IgAN study (NCT04578834). Iptacopan, a B factor inhibitor targeting the alternative complement pathway, demonstrated superiority over placebo in reducing proteinuria (urine protein) in patients with IgA nephropathy and provided a clinically meaningful and statistically significant reduction in proteinuria on top of supportive care. In this study, the safety profile of Iptacopan (200mg, twice daily) was consistent with previously reported data.

Novartis plans to submit a potential accelerated approval application to the FDA in 2024. The study continues in a double-blind manner, evaluating Iptacopan's ability to slow IgAN progression by measuring the estimated glomerular filtration rate (eGFR) slope over 24 months (the primary endpoint at the end of the study, with key results expected in 2025).

Globally, approximately 25/100,000 people are newly diagnosed with IgA nephropathy each year. Up to 30% of IgA nephropathy patients with persistently high levels of proteinuria (≥1g/day) may progress to end-stage renal disease within 10 years. Effective targeted treatments for IgA nephropathy are needed to slow or prevent progression to end-stage renal disease. While current supportive therapies may help slow or prevent the progression of IgA nephropathy to end-stage renal disease, they do not address a key pathogenic step in disease progression: complement system activation.

Iptacopan is currently in development for a range of complement-mediated diseases, including paroxysmal nocturnal hemoglobinuria (PNH), IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), and atypical hemolytic uremic syndrome (aHUS). Based on disease prevalence, unmet needs, and Phase II study data, Iptacopan has received FDA PNH Breakthrough Therapy designation, FDA C3G Breakthrough Therapy designation, FDA and EMA orphan drug designations for PNH and C3G, EMA PRIority MEdicines (PRIME) designation for C3G, and EMA orphan drug designation for IgAN.

With the recent acquisition of Chinook Therapeutics, Novartis has expanded its renal portfolio with two additional IgA nephropathy drugs in development, enriching the existing pipeline.

About the Research

APPLAUSE-IgAN (NCT04578834) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III study designed to evaluate the efficacy and safety of twice-daily oral administration of Iptacopan (200mg) in 470 adult patients with primary IgAN.

The two primary endpoints of the interim and final analyses were reduction in proteinuria (measured by the urine protein/creatinine ratio [UPCR]) at month 9 and the annual estimated glomerular filtration rate (eGFR) slope over 24 months.

References

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3.BarrattJ,RovinB,ZhangH,etal.POS-546EFFICACYANDSAFETYOFIPTACOPANINIgANEPHROPATHY:RESULTSOFARANDOMIZEDDOUBLE-BLINDPLACEBO-CONTROLLEDPHASE2STUDYAT6MONTHS.KidneyIntRep.2022;7(2):S236.doi:10.1016/j.ekir.2022.01.577

4.RizkDV,RovinBH,ZhangH,etal.TargetingtheAlternativeComplementPathwayWithIptacopantoTreatIgANephropathy:DesignandRationaleoftheAPPLAUSE-IgANStudy.KidneyIntRep.2023;8(5):968-979.doi:10.1016/j.ekir.2023.01.041

Editor: Bai Ji

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