Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy

Credit: US Food and Drug Administration

The US Food and Drug Administration has granted accelerated approval to iptacopan (Fabhalta) for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN), according to a release from Novartis.

Announced on August 07, 2024, the approval makes iptacopan the first complement inhibitor approved for the reduction of proteinuria in primary IgAN and is based on interim data from the phase 3 APPLAUSE-IgAN trial, which concluded use of iptacopan was associated with a 38% reduction in proteinuria at 9 months relative to placebo therapy.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, MD, investigator and APPLAUSE-IgAN steering committee member for APPLAUSE-IgAN and professor at the University of Alabama at Birmingham Division of Nephrology.¹ "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."

A rare, progressive kidney disease, the therapeutic pipeline in IgAN has been among the most active of any rare disease in recent years. In 2021, budesonide (Tarpeyo) became the first agent to receive approval for treating proteinuria in IgAN under the FDA’s accelerated approval program, and, in 2023, it became the first agent to receive full approval. In February 2023, sparsentan (Filspari) earned an accelerated approval and awaits a potential full approval before the close of Q3 2024, with a PDUFA date of September 5, 2024. Now, in August 2024, iptacopan has also received accelerated approval.^1,2,3

APPLAUSE-IgAN is a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study launched to assess the efficacy and safety of twice-daily oral iptacopan 200 mg among 518 adult patients with primary IgAN. The primary outcome for the interim analysis was proteinuria reduction at month 9, as assessed by UPCR. The primary endpoint for the final analysis will be the annualized total estimated glomerular filtration rate (eGFR) slope at 24 months.^1,4

Findings from the interim analysis suggested patients in the iptacopan cohort achieved a 38.3% reduction in proteinuria at month 9 (95% confidence interval [CI], 26.0% to 48.6%; P <.0001) relative to placebo. In a presentation of this data at the National Kidney Foundation (NKF) 2024 Spring Clinical Meeting, investigators highlighted UPCR began to decrease as early as week 2, with the most significant decreases observed at month 9 (35.8%; 95% CI 22.6%‒46.7%). Additionally, twice as many patients treated with iptacopan (42.5%; 95% CI, 34.5% to 50.5%) were able to achieve UPCR-24h < 1 g/g at month 9 relative to placebo (21.9%; 95% CI, 14.8% to 29.0%).⁴

According to Novartis, eGFR data from the trial's primary analysis is expected at study completion in 2025. Of note, iptacopan is 1 of 3 renal agents in development programs for IgAN led by Novartis. The others being atrasentan, which received FDA filing acceptance in Q2 2024, and zigakibart, which is in phase 3 development at the time of the August 2024 announcement.¹

"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 and Co-Founder, IgAN Foundation.¹ "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 United States of America. 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 United States of America. August 8, 2024. Accessed August 7, 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. Brooks A. FDA awards full approval to Budesonide (Tarpeyo) in treatment of IGA nephropathy. HCP Live. December 20, 2023. Accessed August 7, 2024. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy.
3. Travere Therapeutics, Inc. Travere Therapeutics announces FDA accelerated approval of FILSPARITM (Sparsentan), the first and only non-immunosuppressive therapy for the reduction of proteinuria in IGA nephropathy. Travere Therapeutics, Inc. February 17, 2023. Accessed August 7, 2024. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-fda-accelerated-approval.
4. Pine L. IPTACOPAN treatment significantly reduces proteinuria in igan. HCP Live. May 17, 2024. Accessed August 7, 2024. https://www.hcplive.com/view/iptacopan-treatment-significantly-reduces-proteinuria-in-igan.