Iptacopan, the First CI, Wins FDA Accelerated Approval for IgA Nephropathy

The FDA has granted accelerated approval to Fabhalta® (iptacopan) for reducing proteinuria in IgA nephropathy (IgAN) patients. Developed by Novartis, this first-in-class complement inhibitor demonstrated a 44% reduction in proteinuria in trials, marking a significant advancement in treatment options for this rare kidney disease.

Novartis announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Fabhalta® (iptacopan), making it the first and only complement inhibitor aimed at reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. This approval heralds a pivotal shift in the treatment landscape that could improve long-term outcomes and quality of life for patients with this challenging condition.

The Path to Approval

Fabhalta achieved a remarkable 44% reduction in proteinuria from baseline in the Phase III APPLAUSE-IgAN study's interim analysis at nine months, compared to a mere 9% reduction in the placebo group. This statistically significant difference of 38% marks a clinically meaningful advancement in IgAN treatment.

“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.

Despite the current standard of care, up to 50% of patients with IgAN—also known as Berger’s disease—and persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis. This rare but serious condition occurs when the immune system attacks the kidneys, causing protein leakage in the urine, known as proteinuria. If untreated, many of these patients may require dialysis or kidney transplantation.

“The heterogeneous and progressive nature of IgA nephropathy has made it challenging to effectively treat this disease. 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,” said Professor Dana Rizk, Investigator and APPLAUSE-IgAN Steering Committee Member.

The drug operates by inhibiting the alternative complement pathway, a component of the immune system that, when overactive, contributes to the deterioration of kidney function in IgAN patients. The FDA's accelerated approval is based on these promising interim results, although further studies are required to confirm the long-term benefits, including a potential slowing of kidney function decline.

Ongoing Research and Future Prospects
The full approval of Fabhalta hinges on the outcomes of the ongoing APPLAUSE-IgAN study, expected to conclude in 2025. This study continues to evaluate whether the drug can slow disease progression as measured by changes in the estimated glomerular filtration rate (eGFR) over 24 months.

Novartis' Broader Commitment
Novartis is also advancing two additional therapies for IgAN, demonstrating a robust commitment to addressing rare renal diseases. These include atrasentan and zigakibart, both of which are in late-stage development and could further revolutionize the care landscape for IgAN.