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Novartis Reports Positive Phase 3 Results for Experimental Therapy to Treat IgAN

October 2, 2023

Rare Daily Staff

Novartis reported positive top-line results from the pre-specified interim analysis of a phase 3 study at nine months in the rare kidney disease IgAN showed it demonstrated superiority to placebo in a clinically meaningful and statistically significant reduction of protein in the urine.

IgAN is a progressive, rare, complement-mediated kidney disease that mostly affects young adults. In IgAN, autoimmune reaction to an abnormal form of IgA results in formation of immune complexes that deposit in the kidney. These immune complexes trigger an inflammatory response leading to progressive kidney damage and loss of kidney function. Up to 30 percent of people who have IgAN with persistent higher levels of proteinuria (≥1 g/day) may progress to kidney failure within 10 years.

Iptacopan is an oral, proximal complement inhibitor that binds factor B and inhibits the alternative complement pathway. Discovered at the Novartis Biomedical Research, iptacopan is currently in development for a range of complement-mediated diseases including paroxysmal nocturnal hemoglobinuria, immunoglobulin A nephropathy, C3 glomerulopathy, immune complex membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.

Based on disease prevalence, unmet needs, and data from phase 2 studies, iptacopan has received FDA Breakthrough Therapy designation in PNH, FDA Breakthrough Therapy designation in C3G, Orphan Drug designations from the FDA and European Medicines Agency in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN23–26.

“These positive data from the phase 3 APPLAUSE study reinforce the potential of iptacopan to provide clinically meaningful benefit to patients with IgAN, a debilitating disease that affects mostly young adults,” said Shreeram Aradhye, president of development and chief medical officer, Novartis.

Novartis said it intends to submit for possible accelerated approval with the FDA in 2024.

APPLAUSE-IgAN is a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral iptacopan in 470 adults with primary IgAN.

The two primary endpoints of the study for the interim and final analysis, respectively, are proteinuria reduction at nine months as measured by urine protein to creatinine ratio (UPCR), and the annualized total estimated glomerular filtration rate (eGFR) slope over 24 months. At the time of final analysis, the following secondary endpoints will also be assessed.

Photo Shreeram Aradhye, president of development and chief medical officer, Novartis

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