Novartis Announces Iptacopan Reduced Proteinuria by 38.3% in IgA Nephropathy Patients in Phase III Interim Analysis

Novartis Iptacopan Phase III Study Interim Analysis Results Released: Significant 38.3% Reduction in Proteinuria in IgA Nephropathy Patients

1.APPLAUSE-IgAN is the first Phase III study to demonstrate that targeting the complement alternative pathway can significantly reduce proteinuria in patients with IgA nephropathy (IgAN). China participated in the global synchronous development of Iptacopan.

2. IgAN is a rare, heterogeneous, progressive kidney disease and a major cause of chronic kidney disease globally; activation of the complement alternative pathway is a key driver of glomerular inflammation in IgAN.

3. IgAN2,5 requires effective targeted therapy; up to 30% of IgAN patients with persistent high levels of proteinuria (≥1g/day) may progress to renal failure within 10 years, requiring maintenance dialysis and/or kidney transplantation6.

4. Novartis will continue to advance its extensive late-stage renal portfolio, exploring the potential to slow disease progression and extend dialysis-free survival.

Recently, Novartis announced the pre-specified interim analysis results of the APPLAUSE-IgAN Phase III study of Iptacopan in patients with IgA Nephropathy (IgAN) at the World Congress of Nephrology (WCN2024). The results showed that, compared with placebo, patients receiving Iptacopan had a significant 38.3% reduction in proteinuria at 9 months (p<0.0001) (measured by Urine Protein/Creatinine Ratio (UPCR)).

Proteinuria is a surrogate endpoint for long-term prognosis in IgAN, and persistent proteinuria indicates poor clinical outcomes. It has been used as a clinical trial endpoint to support the accelerated approval of drugs for IgAN7. The study also showed that Iptacopan was well-tolerated with a favorable safety profile, consistent with previously reported data1,8.

Based on the positive results of the interim analysis, Novartis has submitted a supplemental New Drug Application (sNDA) to the FDA for accelerated approval of Iptacopan for the treatment of IgAN patients, and this application has received priority review from the FDA. If approved, the drug will become the first IgAN therapy specifically targeting the complement alternative pathway. The APPLAUSE-IgAN study is expected to yield final results in 2025 (at 24 months), assessing Iptacopan's ability to slow IgAN progression by measuring the total slope of the estimated glomerular filtration rate (eGFR) over 24 months.

APPLAUSE-IgAN (NCT04578834) is a Phase III global multicenter, randomized, double-blind, placebo-controlled parallel study. China joined the global synchronized development, aiming to evaluate the efficacy and safety of twice-daily oral administration of Iptacopan (200mg) in 443 adult patients with primary IgAN.

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

Iptacopan is an oral targeted complement alternative pathway B factor inhibitor1, currently in development for a range of complement-mediated diseases, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex membranoproliferative glomerulonephritis (IC-MPGN), atypical hemolytic uremic syndrome (aHUS), and lupus nephritis (LN). Iptacopan was approved by the FDA in December 2023 for marketing to treat adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and has received 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 IgAN11-14.

IgAN is a rare, heterogeneous, and progressive kidney disease. It is estimated that approximately 25 people per million are newly diagnosed with IgAN worldwide each year. Up to 30% of IgAN patients with persistently high levels of proteinuria (≥1g/day) may progress to kidney failure within 10 years. There is a clinical need for novel treatments targeting the pathogenesis of IgAN to slow or prevent the progression to kidney failure. Although current supportive therapies may help slow or prevent the progression of IgAN to end-stage renal disease, they do not address a key pathogenic step in disease progression: complement system activation.

Novartis is committed to the field of nephrology

Novartis is exploring potential treatment options through its renal portfolio to address the unmet needs of patients with kidney diseases, including IgAN, C3G, aHUS, IC-MPGN, and LN. In addition to Iptacopan, Novartis China completed the acquisition of Chinren Pharmaceuticals in January this year, which included two drugs in clinical development: Atrasentan and Zigakibart (BION-1301), both for the treatment of IgA nephropathy (IgAN). China has participated in the global synchronized R&D for both products. Novartis has announced positive topline results from the pre-specified interim analysis at 9 months (36 weeks) of the Phase III study of Atrasentan, with full results to be presented next month at the 2024 European Renal Association Congress (ERA)17,18. Novartis’ renal pipeline is committed to developing a series of innovative drugs to improve and extend the lives of patients with kidney disease, benefiting more Chinese patients with kidney conditions.

References
1.PerkovicV,KollinsD,RenfurmR,etal.EfficacyandSafetyofIptacopaninPatientswithIgANephropathy:InterimResultsfromthePhase3APPLAUSE-IgANStudy.PresentedattheWorldCongressofNephrology(WCN);April15,2024;BuenosAires,Argentina.
2.KidneyDisease:ImprovingGlobalOutcomes(KDIGO)2021ClinicalPracticeGuidelinefortheManagementofGlomerularDiseases.KidneyInt.2021;100(4):S1-S276.doi:10.1016/j.kint.2021.05.021
3.RizkDV,MaillardN,JulianBA,etal.TheEmergingRoleofComplementProteinsasaTargetforTherapyofIgANephropathy.FrontImmunol.2019;10:504.doi:10.3389/fimmu.2019.00504
4. Medjeral-Thomas NR, O'Shaughnessy MM. Complement in IgA Nephropathy: The Role of Complement in the Pathogenesis, Diagnosis, and Future Management of IgA Nephropathy. Adv Chronic Kidney Dis. 2020;27(2):111-119. doi:10.1053/j.ackd.2019.12.004 etc.

Disclaimer
1. The aforementioned product has not yet been approved in mainland China.
2. This material aims to provide relevant knowledge in the field of diseases and enhance the level of disease awareness, not for advertising purposes.
3. The information contained in this material is for reference only. Please follow the advice or guidance of doctors or other healthcare professionals.

Editor: Bai Ji

Disclaimer: This article is a reprint from Pharma Intelligence Network. The images and text are the original property of the author, and the purpose of the reprint is to convey more information. It does not represent the views of this platform. If there are any issues regarding the content, copyright, or other aspects, please leave a message on this platform, and we will address it promptly.