Iptacopan Demonstrates 38.3% Proteinuria Reduction in Patients With IgAN

Iptocopan demonstrated superiority when treating patients with immunoglobulin A nephropathy and is the first drug to specifically target the alternative complement pathway.

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About the Trial

Trial Name: Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN)

ClinicalTrials.gov ID: NCT04578834

Sponsor: Novartis Pharmaceuticals

Completion Date (Estimated): October 15, 2025

Results from the phase 3 trial, APPLAUSE-IgAN (NCT04578834), demonstrate that patients who were treated with iptacopan (Fabhalta; Novartis) for immunoglobulin A nephropathy (IgAN) achieved about a 38.3% reduction in proteinuria at 9 months compared with patients who received placebo. The data were presented during a session at the World Congress of Nephrology in Buenos Aires, Argentina, from April 13, 2024, to April 16, 2024.¹

Iptacopan is a Factor B inhibitor of the alternative complement pathway that is administered orally. It was developed for rare diseases including IgAN, complement 3 glomerulopathy, atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis. In December 2023, iptacopan was approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria.¹

IgAN is a heterogeneous and progressive kidney disease. Up to 30% of patients who have the disease have persistently higher levels of proteinuria (≥1 g/day) which may progress to kidney failure within 10 years, and there is a need for effective targeted therapies that can slow or prevent the progression to kidney failure.¹

“IgAN progresses over many years, and patients’ needs may evolve such that different therapies may be best used at different times,” said David Soergel, MD, global head, Cardiovascular, Renal, and Metabolism Development Unit, Novartis, in a press release. “Our renal pipeline includes medicines with a variety of mechanisms which may allow them to be targeted to patients based on their clinical characteristics.”¹

APPLAUSE-IgAN is a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that evaluated the efficacy and safety of iptacopan in patients with IgAN. The 518 patients were randomly assigned to receive either 200 mg of twice-daily oral iptacopan or placebo with supportive care. According to the investigators, the enrolled patients had an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2 or more at baseline, and a smaller cohort of patients with severe renal impairment (eGFR 20-30 mL/min/1.73 m2 at baseline) was also enrolled to provide additional information; however, the data from this cohort did not contribute to the primary efficacy analyses.¹

Further, the study’s primary end points are proteinuria reduction at 9 months (measured by urine protein creatinine ratio [UPCR]) and the annualized eGFR slope over 24 months. Secondary end points include proportion of participants reaching UPCR of at least 1 g/g without the use of a corticosteroid, immunosuppressant, newly approved drugs or background therapy, or the initiation of kidney replacement therapy; time from randomization to first occurrence of composite kidney failure end point event; change from baseline to 9 months in the fatigue scale measured by the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire.^1,2

The pre-specified interim analysis included 250 patients for the efficacy analysis, and 443 for the safety analysis. The trial is currently ongoing; however, interim analysis results demonstrate that iptacopan was well-tolerated among patients and had a safety profile consistent with prior research. Patients who were treated with iptacopan achieved a 38.3% proteinuria reduction (measured by a 24-hour UPCR) at 9 months compared with placebo plus supportive care.¹

“In 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,” said study investigator Dana Rizk, professor, division of nephrology at University of Alabama at Birmingham, and APPLAUSE-IgAN steering committee member, in a press release. “[Iptacopan] is the first potential treatment for IgAN that specifically targets the alternative complement pathway.”¹

References

1. Novartis. New Novartis Fabhalta® (iptacopan) data show clinically meaningful and statistically significant proteinuria reduction of 38.3% versus placebo for patients with IgA nephropathy (IgAN). News release. April 15, 2024. Accessed April 22, 2024. https://www.novartis.com/news/media-releases/new-novartis-fabhalta-iptacopan-data-show-clinically-meaningful-and-statistically-significant-proteinuria-reduction-383-versus-placebo-patients-iga-nephropathy-igan

2. Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN). ClinicalTrials.gov identifier: NCT04578834. Updated January 19, 2024. Accessed April 22, 2024. https://clinicaltrials.gov/study/NCT04578834