Game-changer for kidney disease: Novartis’ Fabhalta wins FDA approval in record time

Novartis has reached a pivotal moment in the treatment of rare kidney diseases with the US Food and Drug Administration (FDA) granting accelerated approval for Fabhalta (iptacopan), a novel therapy designed to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN). This rare, progressively debilitating condition affects the kidneys by attacking the glomeruli, the filtering units, often leading to chronic kidney disease and, in severe cases, kidney failure.

Fabhalta: A breakthrough in IgAN treatment

Fabhalta represents a significant advancement in nephrology, particularly in the management of IgAN, a condition that affects approximately 25 individuals per million each year. The drug targets the alternative complement pathway, a part of the immune system that, when overly active, contributes to the progression of IgAN by causing inflammation and damage to the kidney’s filtering units. Traditional treatments for IgAN have been limited, primarily focusing on managing symptoms rather than addressing the underlying cause. This makes Fabhalta a first-in-class treatment that directly targets the disease mechanism.

The FDA’s accelerated approval was largely based on interim results from the Phase 3 APPLAUSE-IgAN trial, a multicentre, double-blind, placebo-controlled study involving 518 adult patients. The study highlighted Fabhalta’s ability to achieve a 44% reduction in proteinuria after nine months of treatment, compared to only 9% in the placebo group. Proteinuria, the presence of excess proteins in the urine, is a critical marker of kidney damage and a strong predictor of disease progression. Fabhalta’s ability to significantly reduce proteinuria is a promising sign that it may also help slow or halt the progression of IgAN.

Safety and future prospects

Fabhalta has demonstrated a favourable safety profile, aligning with previously reported data from earlier trials. However, its continued approval will depend on the verification of its long-term benefits, particularly its ability to prevent the decline in kidney function. The ongoing APPLAUSE-IgAN study will provide more comprehensive data, including an assessment of the drug’s impact on the estimated glomerular filtration rate (eGFR), a key measure of kidney function. These results, expected in 2025, will be crucial in determining whether Fabhalta receives full FDA approval.

Novartis’ commitment to renal disease care

Victor Bultó, President of Novartis US, emphasized the importance of Fabhalta’s approval, stating that it is a significant step forward in addressing the unmet needs of patients with rare kidney diseases. Novartis has long been committed to advancing the treatment of renal diseases, as evidenced by its extensive research and development efforts in this field. The company is also investigating two additional IgAN therapies, atrasentan and zigakibart, which are currently in late-stage clinical trials. These drugs aim to offer further options for patients, potentially allowing for more personalized treatment strategies based on individual patient profiles.

Expanding the scope of Fabhalta

Beyond IgAN, Novartis is exploring the potential of iptacopan, the active ingredient in Fabhalta, to treat a variety of other rare diseases that involve complement pathway dysregulation. These include C3 glomerulopathy (C3G), atypical haemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN). The company plans to submit applications for FDA and European Medicines Agency (EMA) approval for Fabhalta in treating C3G by the end of the year. This expansion of indications could significantly broaden the drug’s impact, providing new treatment options for patients with these challenging conditions.

Expert opinion on Fabhalta’s approval

Renowned nephrologist Dr. Dana Rizk, a member of the APPLAUSE-IgAN Steering Committee, has expressed optimism regarding Fabhalta’s potential. She highlighted the challenges in treating IgAN, particularly due to its heterogeneous and progressive nature, and praised Fabhalta as a much-needed addition to the limited treatment landscape. Dr. Rizk pointed out that the drug’s targeted mechanism of action offers a new approach to managing the disease, which could be particularly beneficial for patients who have not responded well to existing therapies.

The road ahead

As the final results of the APPLAUSE-IgAN trial approach, the medical community is watching closely. The upcoming data will be crucial in determining Fabhalta’s long-term role in the treatment of IgAN and potentially other related diseases. Novartis’ dedication to expanding the treatment options for renal disease patients, combined with the promising early results of Fabhalta, suggest that this drug could become a cornerstone in the management of IgAN and similar conditions.