Novartis Fabhalta Data Show Statistically Significant Proteinuria Reduction of 38.3% Versus Placebo

On April 15th, Novartis presented results from a pre-specified interim analysis of the Phase III APPLAUSE-IgAN study of Fabhalta (iptacopan), an investigational Factor B inhibitor of the alternative complement pathway, in patients with IgA nephropathy (IgAN). In the analysis, patients treated with Fabhalta achieved a 38.3% (p<0.0001) proteinuria reduction (as measured by 24-hour urine protein to creatinine ratio [UPCR]) at 9 months when compared to placebo on top of supportive care.

Proteinuria reduction is an increasingly recognised surrogate marker correlating with progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated approvals. The study also showed that Fabhalta was well tolerated with a favourable safety profile consistent with previously reported data. Results were presented today during a late-breaking clinical trials session at the World Congress of Nephrology (WCN) in Buenos Aires, Argentina.

“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 Professor Dana Rizk, Investigator and APPLAUSE-IgAN Steering Committee Member and professor in the UAB Division of Nephrology. “Fabhalta is the first potential treatment for IgAN that specifically targets the alternative complement pathway.”

This pre-specified interim analysis included 250 patients for the efficacy analysis and 443 for the safety analysis. The APPLAUSE-IgAN study continues in a double-blind fashion, and therefore only limited interim analysis results can be presented. Submission for possible accelerated approval to the FDA was accepted and has received priority review. The primary endpoint evaluating Fabhalta's ability to slow IgAN progression by measuring the annualised total estimated glomerular filtration rate (eGFR) slope over 24 months is expected at study completion in 2025.

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

Other data presented at WCN include IgAN and C3 glomerulopathy (C3G) real-world studies. Novartis will be presenting further data from the renal portfolio at future medical meetings.

Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway. Discovered at Novartis, Fabhalta is currently in development for a range of rare diseases including IgAN, C3G, atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN).

Fabhalta was approved by the FDA in December 2023 for the treatment of adults with the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH) and received a positive opinion from the CHMP of the EMA in March 2024.