FDA Grants Accelerated Approval to Novartis’ Fabhalta for Primary IgA Nephropathy

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The FDA has granted accelerated approval for Fabhalta (iptacopan), Novartis’ treatment for primary IgA nephropathy. According to the company, the treatment specifically targets the complement system, a key player in IgAN pathogenesis. The approval was based on encouraging results from the Phase III APPLAUSE-IgAN trial, which demonstrated a substantial reduction in proteinuria compared to placebo.¹

"The heterogeneous and progressive nature of IgA nephropathy has made it challenging to effectively treat this disease. Thankfully, the treatment landscape is rapidly evolving," said Dana Rizk, APPLAUSE-IgAN steering committee member, professor, University of Alabama at Birmingham Division of Nephrology, in a press release. "Mounting clinical evidence underscores the pivotal role of complement activation in IgA nephropathy. I am thrilled that this advancement is now available to help enable a targeted treatment approach for IgAN patients."

The multicenter, randomized, double-blind, placebo-controlled, parallel-group APPLAUSE-IgAN trial evaluated the efficacy and safety of twice-daily oral Fabhalta 200 mg in 518 adult primary IgAN patients. The primary endpoints of the study were proteinuria reduction at nine months as measured by 24-hour urine protein-to-creatinine ratio (UPCR) and the annualized total estimated glomerular filtration rate slope over 24 months.

The secondary endpoints—which include proportion of participants reaching UPCR <1 g/g without receiving corticosteroids/immunosuppressants or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating kidney replacement therapy; time from randomization to first occurrence of composite kidney failure endpoint event; and change from baseline to nine months in the fatigue scale as measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire—will be assessed during the study’s final analysis.

Results of the study found that Fabhalta achieved a 44% reduction in proteinuria at nine months related to baseline compared to a 9% reduction in the placebo arm. Novartis reported that this demonstrated a 38% reduction vs. placebo (p<0.0001).

The APPLAUSE-IgAN study demonstrated a favorable safety profile, consistent with previously reported data. Common adverse events (AEs) included upper respiratory tract infection, lipid disorder, and abdominal pain. Potentially serious AEs can be caused by encapsulated bacteria, such as streptococcus pneumoniae, neisseria meningitidis, and hemophilus influenzae type B. Currently, Fabhalta is only available through the Fabhalta Risk Evaluation and Mitigation Strategy program, which requires physician approval to enroll after counseling patients about the risk of serious infections caused by certain bacteria.¹

"Today's approval of Fabhalta as a first-in-class medicine for IgA nephropathy is an important milestone in our journey to evolve rare renal disease care by bringing new treatments to people in urgent need of options," said Victor Bultó, president US, Novartis, in the press release. "We are deeply committed to those living with rare renal diseases and look forward to continued partnership with this community as we further advance our broad portfolio."

According to the American Kidney Fund, an estimated 35.5 million Americans have kidney disease, with a little over 800,000 living with kidney failure. Additionally, over 557,000 people in the United States are currently on dialysis. Statistics show that kidney disease is growing rapidly, as 14% of Americans currently struggle with it.²

"As a parent of a son living with the disease for 20 years, I understand firsthand the fear and uncertainty that come with an IgAN diagnosis, and the devastating impact it can have on patients and their families," said Bonnie Schneider, director, co-founder, IgAN Foundation, in the press release. "Today's approval offers new hope for people living with IgA nephropathy as it represents a treatment innovation that provides us with a new way to fight this multifaceted disease."

References

1. Novartis receives FDA accelerated approval for Fabhalta® (iptacopan), the first and only complement inhibitor for the reduction of proteinuria in primary IgA nephropathy (IgAN). Novartis. August 8, 2024. Accessed August 8, 2024. https://www.novartis.com/us-en/news/media-releases/novartis-receives-fda-accelerated-approval-fabhalta-iptacopan-first-and-only-complement-inhibitor-reduction-proteinuria-primary-iga-nephropathy-igan

2. Quick kidney disease facts and stats. American Kidney Fund. Accessed August 8, 2024. https://www.kidneyfund.org/all-about-kidneys/quick-kidney-disease-facts-and-stats#:~:text=It%20currently%20affects%20more%20than,greater%20risk%20for%20kidney%20failure.